I couldn't see the answer to this question but I know you have to beat certain bosses several times, and I know the fight between Mom's heart is replaced, but how many times do you need to beat the game before you 100% it?
How many times do you need to beat mom and Satan etc to 100% the game
the-binding-of-isaac-rebirth
Related Solutions
The Adversary picks a direction to shoot, then charges up, then shoots. And the homing only goes so far. When you expect him to fire that brimstone, just do a quarter turn around him. Or you can constantly move, circle around him without stopping, and the shots won't get you.
There are five main ways to break the game in Rebirth:
Infinite item charge + Jera + Blank Card. Find a room with batteries/48hr energy pills on the floor, and use the Blank Card w/ Jera to duplicate them. Pick up a battery and infinitely generate more batteries. Now, either you can use this to break using #2, or you can duplicate chests and open them for items. Or, you can use methods described in #3 to get infinite item charge as well.
Infinite drops generation + D20. Abusing Jera is not the only way to create infinite drops. The other major way you can accomplish this is by having coin generation (Swallowed Penny, Piggy Bank, IV Bag, etc.) and infinite health (Scapular, Bloody Penny, Guppy's Paw + Converter, etc.), allowing you to create unlimited money for you to reroll with the D20. A particularly creative way to do this, however, is to have Maggy's Bow (which makes red hearts worth double) and The Jar (which stores red hearts), allowing you to create unlimited red hearts on the floor.
Infinite item charge + D6. This is perhaps the most obvious method. You can get infinite item charges from Sharp Plug or the Habit, but they take health in exchange for spacebar charge, so you'll need a source of infinite health, i.e. Scapular. Another way to get infinite health is Pyromaniac and some sort of bomb item (Dr./Epic Fetus, Ipecac, Kamikaze!), which will give you unlimited healing from the explosion damage.
Greed farming + teleport + D6. Find a secret room or shop with Greed or Super Greed in it. These minibosses spawn enemies, so kill the miniboss while making sure not to kill all the enemies in the room. You can then use any of the free teleport items — Cursed Skull, Broken Remote, etc. — to teleport out of the room and get to fight the miniboss again. Do this a bunch of times until you have plenty of Steam Sales or Quarters in the room, and then you can use the D6 to reroll all of them into useful items. This is by far the slowest and most inefficient way to break the game, but it's also very cheap and easy to pull off.
Undefined. This item teleports you to one of the several special rooms on the floor (item room, secret room, super secret room, I AM ERROR room, and black market). When you have this item in the Chest, you can use it repeatedly and "exit" through the I AM ERROR room trapdoor, looping the Chest forever and getting infinite items. This method is by far the easiest, but also the most unreliable: getting the I AM ERROR room teleport is entirely luck-based, and even if you do get the teleport, you may run out of keys to be able to open any chests. Best used with key-replenishing items like Skeleton Key or the Paper Clip, as well as with infinite recharge items like the Habit.PATCHED IN AFTERBIRTH.
The new DLC Afterbirth added many new ways to break the game, which may or may not be patched in the future. Here are a few of them:
Infinite bombs + restock machine. Get an item that gives you infinite bombs, like Ipecac or Dr. Fetus. Find a shop with a restock machine. Bomb the machine to infinitely reroll the items in the shop until you get the item you want.PATCHED, the restock machine blows up after a whileD7 + D6 + item charge. Find a room with a miniboss that drops an item, like Wrath or Envy (if in the Chest, any room that drops a chest). After beating the miniboss, use the D7 to respawn the miniboss and fight it again. Repeat as desired, and reroll the items with the D6. This was partially patched so that the D7 needed 3 charges instead of just 1, so you'll need a way of charging the item, either with infinite item charges described in #3 or with 9 Volt + AAA Battery.
Angel room + Goat Head + D6 + bombs. Bomb the Angel room statue and beat the Angel that spawns. Take care not to pick up the Key Piece items (the Angels will stop dropping them if you pick one up), and instead reroll them into actual items. Exit the room and reenter for infinite items. Lots of bombs or an infinite bombs item like Ipecac are necessary for this method. Will probably be patched in the future.
Best Answer
Okay because for 100% the answer would be infinite due to the 100% requirements require you to pick up every single item in the game Here are the bare minimum requirements to get every non-RNG boss related task done.
First I am making some assumptions here.
Okay so here we go.
One kill unlocks Mom's Heart.
Killing Mom's Heart 11 times unlocks Sheol and Cathedral (requires 11 Mom kills as well)
Killing Isaac and Satan 6 times each unlock the negative and Polaroid respectively. (Plus 12 to Mom and Mom's Heart kills)
Killing The Lamb and ??? unlocks an item (Plus 2 to Mom and Mom's Heart. Plus 1 for Isaac and Satan.)
Each character after this adds 2 Mom kills, 2 Mom's Heart kills, 1 Satan kill, 1 Isaac kill, 1 Lamb kill, and one ??? kill. Multiply the number of kills listed by 12 and add them to the lists (since we already beat the Lamb and ??? completely with one character.
Giving us:
50 Mom kills
49 Mom's Heart kills
19 Satan and Isaac Kills
13 Lamb and ??? kills
13 Boss Rushes
13 Hush Kills
13 Mega Satan Kills
BUT WAIT THERE IS MORE!
Who could forget about the challenges!
Add 30 Mom kills since every challenge at least requires Mom.
Add 17 Mom's Heart kills taking out challenges for Mom only.
Add 3 Satan kills for challenges ending in Satan (No challenge ends in the Lamb)
Add 5 for Isaac for challenges ending in ??? or Isaac.
Add 1 for ??? for the one challenge ending in ???
Add 1 for Mega Satan due to the challenge ending in a Mega Satan kill.
But what about greed mode?
Well with greed mode we need it to unlock one of our special characters for our completion. Some more assumptions with greed mode.
You are donating 50 coins a run to the greed machine.
You are switching characters regularly to get all the items from greed mode unlocked.
You are playing on Hard.
Okay so now that assumptions of greed mode are done we can do an easy calculation by dividing 1000 coins required for the character by 50 which we are donating every run giving us.
Which will max out our greed machine allowing us to complete the game with all characters.
Which brings us to the moment of truth
To beat all the non-rng content including the main game and challenges you need to kill.
80 Moms
66 Mom's Hearts
22 Satan's
24 Isaac's
20 Ultra Greeds
14 ???s
14 Mega Satan
13 Lambs
13 Boss Rushes
13 Hushes
So it would take between 101 to ∞ runs to unlock beat all of the boss related content 80 runs for Mom and the main game. 20 runs for Greed mode, and one extra run for the Lost.
Technically you could 100% the game in 101 runs if you managed to get absurdly lucky with RNG and manage to pick up every possible item in the game during your time playing but this is nearly impossible to happen.
Good luck trying to get only 101 runs to unlock all the content!