The Guardian

The Guardian is a new challenge added in The Binding of Isaac: Afterbirth. Isaac starts Blindfolded, with Punching Bag, Isaac's Heart, Holy Grail, and Spear Of Destiny. The goal is to defeat Mom's Heart or It Lives. Isaac's Heart will follow the Punching Bag instead of Isaac.

Difficulty

The main difficulty of this challenge stems from the fact that Isaac's health is damaged when the Punching Bag is hit for any reason (due to Isaac's Heart), and that the Punching Bag will move of its own unpredictable accord, severely hindering the player's agency in avoiding damage. This makes The Guardian one of the tougher challenges in the game.

Note since it's the Punching Bag who takes damage, and it doesn't have flight, the Punching Bag is not immune to spikes and creep as Isaac's Heart would be. The lack of Treasure Rooms and tears only further compounds to the difficulty, to the point where certain rooms and bosses, which can be normally completed without taking damage, may now guarantee substantial amount of unavoidable damage. For example, Red Champion Mom is almost impossible to clear as she will always target Punching Bag.

Strategy

The player should follow a general priority in which enemies to kill: enemies that run towards the Punching Bag, followed by exploding enemies, followed by enemies with piercing shots (i.e. Enemies that fire Brimstone shots), followed by enemies that fire regular shots. Remember that Isaac himself is invincible, allowing him to "body-block" shots flying towards the heart.

Rooms containing Mom's Hand are almost impossible to clear (because the Punching Bag is incapable of dodging them), and should be skipped whenever possible. Bombs can be used to skip these rooms by bombing doors open.

It may be better to go for Angel Rooms rather than Devil Rooms in this challenge, since they may offer invaluable items like The Bible, The Wafer, and Breath of Life at the cost of no health.

Finding or buying The Bible makes the challenge a lot easier, allowing Isaac to instantly kill both Mom and Mom's Heart.

As the red champion version of Mom is nearly impossible to get past normally, a lot of Health, The Wafer, or Chaos Card are necessary if Isaac doesn't have The Bible (or if it isn't fully recharged).

Spend as little time as possible in rooms with spikes, because there's a high chance the Punching Bag will walk into them.

Orbitals are extremely useful for this challenge, since most of them deal a good amount of damage on direct contact. Items such as Sacrificial Dagger are the best source of damage. Health is also important to make up for unnecessary damage, as is Speed to rush towards enemies and destroy them before they can attack Isaac's Heart. Also, pick up the Error: The given collectible ("Humbling Bundle") does not exist. for its double Red Hearts.

Isaac can use the spear's fear effect to his advantage and force bosses and mini-bosses away from Punching Bag. This is especially effective against bosses that chase Punching Bag, such as Gemini or Lust.

If the player are not too concerned with time or score and just want the unlock, Placenta is a good item to get as well since it can regenerate Isaac's health. A much, much slower way can be done by obtaining Mysterious Candy, which randomly spawns Poops. Destroying poop can drop Half Red Hearts and Soul Hearts.

The Breath of Life can be extremely helpful in completing this challenge. Isaac's Heart will enable the spacebar indefinitely and not take damage, while doing so will make Isaac completely immune to damage. He still can be hurt while the charge bar is still depleting after entering the room, but it does make things easier, especially with bosses, and allows him to explore rooms with hazards such as spikes without having to worry that the Punching Bag will wander into them.

It should be noted that Isaac can transform into Guppy during this challenge even though the visual change that accompanies the transformation are not shown, and he will be able to make flies. The Spear of Destiny does not generate flies, but familiars and items that generate tears, such as Tammy's Head and Incubus, will.

Obtaining Blood Rights basically wins the challenge as it can be spammed while annihilating everything inside (with the exception of Hosts and Cod Worms). But since there are no Treasure Rooms present, it can only be obtained via a lucky Crawl Space or room generation.

Having a second player join in makes the game significantly easier. A co-op baby has its own Spear of Destiny and is not blindfolded so is able to shoot tears as normal. The co-op baby doesn't take damage because of Isaac's Heart.

Obtaining Athame allows Isaac to activate the black brimstone ring without taking damage, which would make cleaning a room a lot easier, and spawn more Black hearts.

Obtaining The Virus allows Isaac to inflict poison upon enemies without taking damage and get Black Hearts sometimes after killing enemies.
- The Virus and other poisoning effects are useful against enemies such as Walking Host, Cod Worm, etc, as they can remain invulnerable to the Spear of Destiny and still deal contact damage to the Punching Bag.

Familiars such as Lil Brimstone, The Relic, Dark Bum, Little C.H.A.D., Incubus, and Succubus (especially when combined with BFFS!) will make the challenge easier.

One Makes You Small pills can make the challenge much more difficult, as the decreased hitbox makes it harder to block the Punching Bag from attacks.

Book of Shadows also makes the challenge significantly easier as it can be activated in order to prevent Isaac's Heart from taking any damage for 10 seconds.