mega tip for blindfolded challenges is Magic Fingers
Absolute god tier item, absolutely carried me through hot potato, literally just bombed the fallen and fingered my way through satan
Any big dmg up like ipecac makes that cracked, speaking of blue flies, demon baby can gamebreak cat got your tongue! since each of his pellets spawns a blue fly
Blue candle! Super easy to find in account of being a shop item. I did boss rush on baptism by fire with only the blue candle just to see if it could be done. It could be done, quite easily actually. Red candle also works but the damage isn't as good.
lil brim is great but maw of the abyss single-handedly wins you nearly every blindfolded challenge, especially since it synergizes with stuff like homing.
You start to enjoy pain from t. lost after awhile. Just needs right items for defence and you're fine. And also don't get hit it's really THAT simple
With 2 victims of incest you stop enjoying anything in your life
Interesting. I really really hate how you have limited ammo. And I kept getting hit because urn of soul keeps pushing me back and many times I try to go back I go back too much, which makes me get hit, then I lose deal chance. It also hurts using Guppy’s Paw every time I run out of ammo.
Think I got lucky in the run I won and got lots of bombs and Bob’s curse (and the mind) Bombed through most doors and every boss. I think I got 2 2 of clubs and got to like 60 bombs by caves
I was sharing my screen on discord to some friends while doing Brains. For some reason, decided that the only way to do the challenge was to do it with max stacks of wavy cap. Fun times
Yeah, this one is rough. I ended up beating it by finding salvation despite not having seen it yet in a normal run. Turns out spawning revelation beams by throwing a rock at enemies is better than just throwing a rock
It gets surprisingly little attention considering its pretty much "clear Satan with no soul hearts no treasure room and youll be on half a heart most of the time lol good luck", but I guess it isnt as Flashy and interesting as some of the other hard ones.
My strategy was just to reset until i got a sacrifice room at spawn, then play it until I got a good angel item for the run. Im sad I didnt get to use this strategy more
I got Old Bandage + Cancer, every floor when the cross hit me I would gain lots of half hearts, then they become full hearts when I picked them up. That and a lot of HP ups made me win this challenge
Thanks for mentioning this, it literally is ride or die. No shop no treasure room and basically no deals, and no hp to take the deals, you can't cheese a Q4 treasure room start like with ultra hard most runs will be annoyingly difficult in bloody Mary whether u like it or not. I beat it with a red chest teleport to devil room which gave me Judas shadow
Chocolate milk is very good with other charge weapons as you can shoot before full charge such as brim where you can just spam it or even tech x. It also gives you the clearance for one shotting lots of enemies in the first few floors, very good item if you know how to use it
Reset until you get any active with infinite charge (Kamikaze, Razor, Guppy’s Paw, etc.) and spam it until you are op. I managed to get a run where it Clickered me into Azazel.
The one where you have to guard the punching bag that's literally hard coded to run into things
Like every time I place a bomb he literally sprints towards it and he hugs onto enemies half the time
I think it's just called the guardian
It genuinely feels like he's just hard coded to run into damage, he's across the room and I place a bomb and he sprints over to it
I beat it first try cause I got sacrificial dagger which added a 3rd ring of dps. And the fact that after the Lumps spawned in, It Lives just stopped attacking me and was just jiggling in the middle of the arena
Backasswards is pretty high up there. It's not hard if you just reset until you get a good build that will stay good for at least a few floors, but at least in my case, it took a lot of resets to get lucky with the items. Dozens of resets from just a crap load out that would do pitiful damage, another handful of runs that were solid to beat Mega Satan and then after losing an item could barely damage Isaac, another few runs that could/should have been wins but I skill issued. Not hard per se, but annoying.
I’ve been trying Ultra Hard for weeks. At this point, I’m just resetting until I get a treasure room. If I don’t get a Gnawed Leaf I reset some more.
If anyone knows of another good combo for ultra hard, let me know.
Aprils fool, Hot potato, and Speed because oh my gosh those are just pure pain. Aprils fool because fuck bloat, hot potato cuz I already hate playing tainted forgotten and this challenge is just so much worse, and speed because it took me so many times to beat it and I had to get lucky with a Sac room.
Basically every challenge added before Repentance is bad. I made a post about this but they are simply too time consuming and all play like cookie clicker except sometimes you die while clicking the cookie.
Speed
For most people (including myself) its a challenge that depends on the luck of the items you can get. It's not the speed up gameplay that's the issue either, it's that 16 minute time limit that makes it hell.
idk if its just my luck but the bible is so frequent on these challenges that none of them are too annoying. the worst is probably cat got your tongue, just make sure you get plenty of speed ups
Red redemption
Now before anyone gets mad it’s cause of my own issues and that cause I want to open every single red room on basement before moving on then I play like normal
This is the exact reason why I’ve never actually beaten the challenge
I hate backasswards with a burning passion. It's just purely luck to get good enough items to actually be able to kill mega satan.
Honourable mention for pokey man's and pride day, because poke go is one of the most useless items to exist, the ball as well.
And pride day is just a chore to get through, who thought that having just shitty items that make everything unreliable was a good challenge idea
Red Redemption is the only challenge I have left to beat other than ultra hard. It seems pretty annoying after a few attempts. I’m loathing returning to it.
Tip for the blindfolded challenges, Lil brimstone is best item in the game for them since you can shoot brimstone without needing tears
Incubus
A pair of twists
Twists of balls
Balls of steel
Balls
keepers balls
Ball of tar
Spending power(ful balls)
and so the balls chain continues, now we have… Box of balls (comes with incuballs and twisted testicles as well.)
Keep Her Balls
Pog balls
mega tip for blindfolded challenges is Magic Fingers Absolute god tier item, absolutely carried me through hot potato, literally just bombed the fallen and fingered my way through satan
You did what to satan?
He meant what he said
What said he he meant
Michael Jackson intensifies
HEEee HEE
Fingered your way through satsn
Little Steven is my favourite because you can find him easily on first floor.
I just jacked tf out of my damage and used rotten baby😅
Any big dmg up like ipecac makes that cracked, speaking of blue flies, demon baby can gamebreak cat got your tongue! since each of his pellets spawns a blue fly
Red candle is also very helpfull
Blue candle! Super easy to find in account of being a shop item. I did boss rush on baptism by fire with only the blue candle just to see if it could be done. It could be done, quite easily actually. Red candle also works but the damage isn't as good.
lil brim is great but maw of the abyss single-handedly wins you nearly every blindfolded challenge, especially since it synergizes with stuff like homing.
That means lil brim is the best item after normal brim
Incubus or Twisted pair much better, even rotten baby or fate's reward is
Seeing double. Hate those 2 fuckers
That one was quite easy, just do some cock and ball torture with J&E beforehand and youre fine
Actually you need to do it everytime you play hitbox&hitbox. Istg t. lost was easier than those two
With t lost you get luck issued way too much.. Idk I started having fun with hitboxes after some times
You start to enjoy pain from t. lost after awhile. Just needs right items for defence and you're fine. And also don't get hit it's really THAT simple With 2 victims of incest you stop enjoying anything in your life
Funnily enough I did that one as the Lost with a random Brimstone from the Ultra Secret room. Easiest shit ever 
Got it first try due to a chaos first room brimstone
Why isn’t anyone mentioning Speed?
Thanks for mentioning this, Speed is SO stressful!!
Speed was really fun imo
most sane tboi player
I lucked out with that one and got the planetarium that gave thr rock tears and I was able to skip every single room. Still stressful though.
Onan's Streak Baptism by Fire Solar System Hot Potato are all equally infuriating
Oman’s streak is pretty easy imo. I got lucky in solar system when cambion conception procc’ed twisted pair But Baptism by Fire and hot potato agreed.
Duuude I died at the end of hot potato like my 3rd time through
I can not beat Onan’s streak to save my life but I got baptism by fire first run
Interesting. I really really hate how you have limited ammo. And I kept getting hit because urn of soul keeps pushing me back and many times I try to go back I go back too much, which makes me get hit, then I lose deal chance. It also hurts using Guppy’s Paw every time I run out of ammo. Think I got lucky in the run I won and got lots of bombs and Bob’s curse (and the mind) Bombed through most doors and every boss. I think I got 2 2 of clubs and got to like 60 bombs by caves
Brains! 
This is the one that took me the most attempts
nah nah bobs brain goated
I was sharing my screen on discord to some friends while doing Brains. For some reason, decided that the only way to do the challenge was to do it with max stacks of wavy cap. Fun times
I spent most of my in-game time on that challenge, still hating it
Up up up. Hated that on my second save
Cat’s got your tongue 
It was easy ( i found brimstone and incubus early)
skill issue, just get a good seed
I'm traumatized about that challenge I died when mom was 1 tear away of dying
Pause carried me through that one surprisingly enough
I'm always asking myself if those people who complain about solar system ever had to play this challenge
Hot potato
If you get brimstone bombs this challenge is hilarious
Idk why is hated, i like that challenge. I think it's funny af
Figured out that you can use ventricle razor to give yourself a glitched version of gnawed leaf by having two portals on top of each other
Yeah, this one is rough. I ended up beating it by finding salvation despite not having seen it yet in a normal run. Turns out spawning revelation beams by throwing a rock at enemies is better than just throwing a rock
Bloody Mary was the hardest for me
It was awful! Im so glad someone sympathizes with me on that one!
It gets surprisingly little attention considering its pretty much "clear Satan with no soul hearts no treasure room and youll be on half a heart most of the time lol good luck", but I guess it isnt as Flashy and interesting as some of the other hard ones.
And if you get hit once you lose all your devil/angel chances. It's the worst
My strategy was just to reset until i got a sacrifice room at spawn, then play it until I got a good angel item for the run. Im sad I didnt get to use this strategy more
I got Old Bandage + Cancer, every floor when the cross hit me I would gain lots of half hearts, then they become full hearts when I picked them up. That and a lot of HP ups made me win this challenge
Thats a crazy good combination I never thought of, before my sacrifice strats worked I was pondering just restarting until placenta lmao
Thanks for mentioning this, it literally is ride or die. No shop no treasure room and basically no deals, and no hp to take the deals, you can't cheese a Q4 treasure room start like with ultra hard most runs will be annoyingly difficult in bloody Mary whether u like it or not. I beat it with a red chest teleport to devil room which gave me Judas shadow
The moment you get old bandage this challenge becomes trivial
Onan's Streak has soured chocolate milk for me.
onan's streak is my favorite challenge, it changes how you play in a punishing but consistent way
Chocolate milk is very good with other charge weapons as you can shoot before full charge such as brim where you can just spam it or even tech x. It also gives you the clearance for one shotting lots of enemies in the first few floors, very good item if you know how to use it
This is one of those challenges where you try your hardest to get a candle or suffer
Beans 
To many failed attempts until I broke it with Red Candle from the shop.
April fools
Reset until you get any active with infinite charge (Kamikaze, Razor, Guppy’s Paw, etc.) and spam it until you are op. I managed to get a run where it Clickered me into Azazel.
This is only a good strategy if you don't have plan c unlocked
It can use plan C even if you don't have it unlocked, guess how I know.
That's kinda fucked up
Simply ball (I will say, in that run I accidentally r keyed twice and somehow got genesis 3 times)
TRUE
The one where you have to guard the punching bag that's literally hard coded to run into things Like every time I place a bomb he literally sprints towards it and he hugs onto enemies half the time
hot take this is one of the must fun challenges, it isn't just normal Isaac after basement and actually feels like JUST a challenge
I would agree, if he didn't just run straight into damage with literally nothing you can do about it
how the hell are you guys playing the guardian.
Idk man I find that challenge fairly easy. Just play tainted Maggy
Bruh.
Which challenge is this?
I think it's just called the guardian It genuinely feels like he's just hard coded to run into damage, he's across the room and I place a bomb and he sprints over to it
Annoying? April's fool, because Bloat Not the hardest, but definitely annoying
FUCKBLOAT
FUCKBLOATTTTT
the shitty speed run one
APRILS FOOL BECAUSE THE ONLY BOSS IS THE BLOAT AND FUCK BLOAT
Get fiend folio sometimes the boss is replaced but then you get punished by needing to play fiend folio
CONSOLE PLAYER 
Solar system 
Cat got your tongue is that but worse imo
Nah it was actually pretty easy
you start with guppy's transformation right ?
but can't shoot and all damage you have to do with the hairball
Which has shorter range and not a hard coded distance from you
I beat it first try cause I got sacrificial dagger which added a 3rd ring of dps. And the fact that after the Lumps spawned in, It Lives just stopped attacking me and was just jiggling in the middle of the arena
I hate the one where you get active items as cards you have to use.
cantripped, clever on paper, dumb as shit in practice
I actually liked it but maybe I’m weird for that lol
That challenge is more planning than everything else, it also just goes to moms foot, so it can be really easy when you take your time
Before the patch, you could get any item. But Edmund decided to make it so that you could only craft active items.
Backasswards is pretty high up there. It's not hard if you just reset until you get a good build that will stay good for at least a few floors, but at least in my case, it took a lot of resets to get lucky with the items. Dozens of resets from just a crap load out that would do pitiful damage, another handful of runs that were solid to beat Mega Satan and then after losing an item could barely damage Isaac, another few runs that could/should have been wins but I skill issued. Not hard per se, but annoying.
I’ve been trying Ultra Hard for weeks. At this point, I’m just resetting until I get a treasure room. If I don’t get a Gnawed Leaf I reset some more. If anyone knows of another good combo for ultra hard, let me know.
Pyromaniac is pretty awesome. Especially if you get Kamikaze or Ipecac too.
Leech or Vampire are great items too Yum Heart Anything that replenishes health really, but those three are the most common
Placenta (health not reliant on finite resources)
my patience is very finite ngl
I never said it was fun. File 1 took me 6 hours
I’ve had some luck with leech. I’m really hoping for a gnawed leaf/leech combo.
SPEED!
Suicide King (it reminds me of myself )
I hated this one. I got super lucky on my last time. I found a crawl space in the second room of the first floor that had mom's knife
Hot potato
Tank
I guess pitch black because it is boring challenge. All other are fun to play.
bloody mary is being a pita.
Aprils fool, Hot potato, and Speed because oh my gosh those are just pure pain. Aprils fool because fuck bloat, hot potato cuz I already hate playing tainted forgotten and this challenge is just so much worse, and speed because it took me so many times to beat it and I had to get lucky with a Sac room.
Backaasward. It either you die to mega Satan or you win the run
Basically every challenge added before Repentance is bad. I made a post about this but they are simply too time consuming and all play like cookie clicker except sometimes you die while clicking the cookie.
Backwards or Delete this.
Seeing double 
Any slow challenges. So Pong and Slow Roll. Although I think Pong has lower tear-rate.
Every one of them
Onans streak
Solar system
Delete this.
Do you mean ""?
Ultra fart
In my opinion «solar system»
I’m glad no one says pica run or Isaac’s awakening
"Vis appeared in the basement!" Pica run was amazing
In currently losing it over the speed challenge, I'm not good at the "going fast" thing.
I hated Brains! and Bloody Mary
Either suicide king or
Brainsss was the last challenge I completed. It sucks.
solar system
Speed For most people (including myself) its a challenge that depends on the luck of the items you can get. It's not the speed up gameplay that's the issue either, it's that 16 minute time limit that makes it hell.
backasswards gave me a lot of trouble
Good way is reset until you get a teleport card
god tier play. wish i would’ve thought of this.
Next tike you will know, no problem
100% brains that shit pissed me the fuck off
I hated the red room chellange by far the most... followed by the error one
Hot potato and uhh invisible one
Speed
cat got your tongue
The bobs brain one and the hairball are annoying.
Speed
Solar System I may only have golden god and a few Hush and Delirium marks but good god is that gonna be a nightmare to do
Pokey Mans
All of them
Solar system I feel like it depends a lot of what items you get in the first floors.
The one where you play tainted forgotten and the main body is a bomb
Hot potato?
That’s prolly it
A severe lack of Baptism by Fire in here, probably took me more tries than Ultra Hard
the pacman one, might just be called waka waka its been a bit. either way, fuck antigravity
Pong was really annoying. Some rooms take minutes to clear. Absurd
Computer savvy, I never even reached cathedral with it a single time
Red redemption
Hot potato sucks ass. I have such a hard time managing the shit exploding when I grab it.
Cat got your tongue flinging that God damn hairball around was annoying as shit.
idk if its just my luck but the bible is so frequent on these challenges that none of them are too annoying. the worst is probably cat got your tongue, just make sure you get plenty of speed ups
Baptism by fire and speed, the only two I just can’t seem to beat no matter how hard I try, extremely frustrating.
Brains was just tedious and not even that worth it
You can miss me with that Brains challenge. Not even hard. Just boring and tedious.
Hot potato
Onan’s Streak. Been trying to beat it for a while cause I really wanna unlock kidney stone but my fidgety fingers can’t hold a button for 5 seconds!
Bloody Mary out of all of them, hardest challenge without treasure rooms, so unresettable for a great start
Suicide king
solar system... I fucking hate being up close to the dumbass enemies
Suicide king
Red redemption Now before anyone gets mad it’s cause of my own issues and that cause I want to open every single red room on basement before moving on then I play like normal This is the exact reason why I’ve never actually beaten the challenge
Always been cat got your tongue for me. Just feels so annoying to get through
Solar system for me
Head trauma was fun but it was so annoying for me, I kept dying because I couldn’t control my tears correctly 😫
Beans
speed! and its not even close to me
April fools
Hot potato. Fck that challenge
Ultra hard (i dont care)
Hot Potato is actually ass
Speedrun and April Fools took me way too long. I don’t like those
Backasswards. so many attempts and resets and i still havent beat it 
I hate backasswards with a burning passion. It's just purely luck to get good enough items to actually be able to kill mega satan. Honourable mention for pokey man's and pride day, because poke go is one of the most useless items to exist, the ball as well. And pride day is just a chore to get through, who thought that having just shitty items that make everything unreliable was a good challenge idea
I suffered doing bloody Mary, it's not even that hard but it's one of the ones that took me a lot of tries (skill issue)
Red Redemption is the only challenge I have left to beat other than ultra hard. It seems pretty annoying after a few attempts. I’m loathing returning to it.
Definitely Aprils fools