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You can't take Devil Deals except uncommon circumstances where you have HP ups lying around or a Strength Card, so Angel Deals are much better. Especially in Afterbirth+.
It's better to look for a way to reroll items/the entire run where most items you pick up are going to be functionally useless, such as HP up.
Focusing on DPS items and orbitals will make Keeper runs easier, just get lucky. Keeper can get very strong when you find more and more damage ups where flies appear often from health pickups.
Playing defensively is the best way to play Keeper, don't overextend Devil Deals, Curse Rooms or even normal rooms can since they can potentially kill Keeper very fast. Flight also helps mitigate Keeper's slow speed, and enables the strategy of playing defensively like you would do the Lost. Orbitals are essential playing defensively, or even offensively.
Risk-taking as Keeper is questionable. Taking a Devil Deal ususally won't provide much benefit since many deals don't carry a Keeper run and the risk is compounded by no Angel deals. But Succubus, Rotten Baby and Guppy Items can be very helpful.
Keeper can get money very quickly through Wooden Nickel and infinitely playing Blood Banks for spare nickels/dimes, so shops are essentially free for finding survival items or items for breaking the game. Store Key mitigates key famines allowing free access to shops.
Secret Rooms and Super Secret Rooms are deceptively amazing. Pickups in the secret room, heart pickups turned to flies or rare rune rooms in the super secret room can help immensely.
Keeper is a slow character. His runs will be slow. Boss Rush can be important but usually isn't worth the risk unless you have Swallowed Penny, a teleport item/card or something like that. If you got to do it, you've got to do it. Hush usually requires significant skill and/or luck. Delirium on a larger scale.
Thanks for your answer, this seems really helpful!
I think I'll try the defensive route, I always tried to get the best offense (that's how I beat this game with the Lost) but it makes sense to have damage-blockers.
And I'll try to go for Angel Rooms instead.
But what are DPS items?
Still... with all this info it goes back to RNGesus)
Blood banks nah, and are still useful for generating free nickels/dimes. Also, I would prefer to play on AB+ solely because of the restock machines in shops, force out something like sack head, 1+1 pickups, restock, hive mind with all that excess money for getting lucky and playing well.
So hold R until you Start in the Cellar and find swallowed penny under some pots, then Go.
Sadly, most things everyone said is stuff I already tried.
So It's really like some say, git gud xD
I have not tried using the angel room so I'm going to try that.
Well, back to re-rolling till I get some good items
It's good for potential game-breaks/farming for resources, but if you run into a room where you're getting hit quick, it's easily possible that you'll get hit a second time before you can pick up the first coin.
It's not by any means a game-winner, even though it's often trotted out as THE Keeper item.
Take your time. Given that Keeper is slow and overall very below average, it makes sense to get as much value as possible out of each floor, especially the first two floors. Once you hit Caves/Depths, there are plenty of 'game over' rooms for the Keeper unless you've significantly upgraded him.
Something I don't often see mentioned that I've found is an solid advantage for Keeper is playing Sacrifice Rooms. Don't pick up coins unless you need them to heal, so you have a lot of effective HP lying around.
The 6th play on a Sacrifice Room has a 33% of teleporting you to the Angel Room for that floor, and the 7th play has a 33% chance of spawning an Angel Room pedestal item in the Sacrifice Room.
Angel items will also give you a good chance to get the Seraphim transformation, which grants flying (and in turn, gives the Keeper huge survivability on a lot of difficult rooms).
When I was going for Keeper completion marks, I'd restart, check the item room, and check for a Sacrifice Room on the first floor. Anything decent from the first item room is worth going for. I'd even be happy with a Dead Onion (piercing and spectral is great) start or a Roid Rage start (1/3 Spun and enough speed to dodge virtually anything in the game).
Mom, it lives, Isaac and Lamb was easy.
With the sacrifice rooms you can get BOTH Key pieces in the first floor if you can find enough coins. Boss rush with swallowed penny is pretty easy too.
Hush is all about DPS. 2-3 orbitals, speed and Tons of damage was my Set up.
Mega Satan is pretty easy even with an medicore/decent build.
But yeah, good first item room like magic mush or death's touch, sacrifice rooms and swallowed penny and your good.
Important are your dodging skills :)