The Binding of Isaac is one of the biggest roguelikes around, and for a good reason. With hundreds of items at your disposal, the possibilities are endless. No run will be the same due to how many synergies there are between those items. Over the years, the game has added so much more to the base game through DLC that added new items, enemies, bosses, rooms, characters and so much more.
To add to all of this variety the game also offers 11 characters in the base game with a total of 23 if you also have all the DLCs. The caveat is that some of those characters have special mechanics that will make your runs even harder. But let's find out which of these characters will actually give you extra breathing room when trying to learn the game.
6 Magdalene
Magdalene is one of the characters that came with the base game and can be unlocked by getting seven or more heart containers in a single run. She starts out with four heart containers and the Yum Heart spacebar item which heals you for one heart container upon use. If you've managed to complete the Aprils Fool challenge run, she also gets a full health pill. Her other stats are pretty close to average, except for her move speed of 0.85 which is below the average that other characters have.
Her one big advantage at the start of the game is that she has more HP to use in a Devil Deal. Even though she has the most HP out of all the characters when starting out, you have to pay careful attention to picking up items that negatively affect your movement speed. Going any lower with it will make it impossible to not get hit when facing enemies that move quickly or fire fast-moving projectiles.
5 Samson
This character, inspired by a biblical hero, can be unlocked by defeating two floors in a row without getting hit. He starts off with three red heart containers and the Bloody Lust item, which increases Samson's damage any time he receives damage. Be aware of the fact that the bonus damage will reset after you leave the current floor. After completing the Ultra Hard challenge, Samson will also start the game with the Child's Heart trinket which will increase his chances of finding red hearts.
Due to his damage increasing when he gets damaged, Samson synergizes well with the usage of Devil Beggars, Sacrifice Rooms, and Blood Donation machines. Any spacebar items that hurt your character such as IV Bag, Blood Rights, Razor Blade, or Sharp Plug also work well with Samson.
4 Eve
Another character that you need to unlock by beating two floors in a row without collecting any hearts, Eve starts out the game with two heart containers and the Whore of Babylon and Dead Bird items. Whore of Babylon will increase your damage when you have only one HP left and Dead Bird will spawn a small bird helper that will attack enemies until you leave the room. After donating 439 coins to the Greed Donation machine, Eve will also start out with the Razor Blade spacebar item, which will allow you to enable the Whore of Babylon effect from the get-go.
Similar to Samson, Eve thrives when on low HP, even though this leaves her vulnerable. In order to fix this, you should focus on finding as many Soul Hearts as possible on the first few floors. Another easy way to keep your Whore of Babylon effect up all the time is giving up one of your heart containers in a Devil Deal room.
3 Cain
Cain can be unlocked if you donate 55 or more coins at once in a single run, which is trickier than you might expect since the Donation Machines have a chance to explode after every coin you put in. He has two heart containers, one key, and the Lucky Foot item which gives him +1 luck, better chances when playing any of the Arcade games, and converts all bad pills in your run into their good counterparts. After the Greed Donation machine has 68 coins or more, you will also start with the Paper Clip trinket, which will open golden chests without using a key.
Out of all the characters on this list, Cain has the most starting damage and speed, making him especially strong in the early game. If you've unlocked the Paper Clip, then consumables shouldn't be a problem since you can open up all golden chests that you encounter. This also increases your odds of finding some strong items from the golden chest pool like Guppy's Head or Cricket's Head.
2 Azazel
This little demon baby can be unlocked by making three Devil Deals in a single run. He starts out with some excellent abilities in the form of a short-range Brimstone and flight. To balance this out he starts the game with three Black Hearts and no heart containers. You will also start with a 0 - The Fool card which can help you out of a sticky situation.
In the right hands, Azazel can literally reach the endgame without any other items except his starter ones. You should mostly focus on increasing his attack range to make his Brimstone fire further and getting as many heart containers as possible to ensure survivability.
1 Isaac
The titular character of the game, Isaac is unlocked by default. He starts the game with three red heart containers and one Bomb. After you defeat the final Isaac boss with Blue Baby you will also start the game with the D6.
Even though Isaac has average stats and starts with only the D6, he is by far one of the strongest characters in the game. The fact that you can reroll any bad items that you get throughout your run is extremely powerful, especially when you encounter Devil Deals that have multiple items. He also synergizes very well with items that drop batteries or items that charge your D6 faster.