This page is for the comparison of items that are similar, in use or purpose, to find what items are most useful in which situations, and successful item combinations.

For combinations of items that modify the player's attack projectile, see the Item Synergy page.

Guppy vs. 1UPEdit

Guppy: Available in the Devil Room for 2 Hearts. Gives 9 lives but cuts health down to 1 container regardless of heart containers remaining from the purchase.

1UP: Available in Treasure rooms and Secret Rooms. Gives 1 extra life.

Both items enable the player to die at least once with almost no consequence, except the enemies in the room the player died in re-spawn if not killed. However, Guppy limits the player to one heart container, making death much more likely for them. They have nine lives, giving a player nine chances. This is recommended for players with a Book of Revelations or any Soul Heart adding Items, and are experienced with dodging. Having Pretty Fly or Meat Cube, or any blocking items may help a lot while using Guppy. 1UP is more easily accessed, and doesn't remove any heart containers. It's an easier option, and much easier for defense-challenged players, but does have the notable drawback of only working once.

There is the plus with Guppy that in Devil Rooms you are able to go to negative hearts to sacrifice for an item. Simply dying can reset your hearts to one, allowing you to clear out a devil room with no ill-effects. This should not be attempted with a 1UP which also allows you to clean the room but dying will leave you with the same amount of hearts you had when you died.

Guppy is least determental with ??? Because ??? never had any natural health to begin with, meaning that you don't lose as much on respawn, but starting at only 1 soul heart is still difficult.

Book of Shadows vs. My little UnicornEdit

Book of Shadows: Can shoot Tears, dealing no damage to enemies, 3 Rooms need for Recharge

My little Unicorn: Can't shoot Tears, deals heavy damage to enemies, 6 Rooms need for Recharge

Both Items grant Invincibility, but My little Unicorn is a item preferred for Players which are using Familiars and The Virus more often. The Book of Shadows is preferred for defense players with high stats or tears increasing items like The third Eye or Number One.

Note: Because of a bug, My Little Unicorn grants multiple throws of Mom's Knife instead of preventing the use of it.

Pill Popper ComboEdit

Mom's Bottle of Pills: Spawns a random pill.

Battery: Gives up to 3 extra item charges per battle (depending on how long the battle lasts). Using an item resets the charge, allowing a maximum of 6 bars to be charged per battle. With enough patience, all items can be used once per room.

PHD: Changes the effects of the Health Down, Tears Down, Speed Down, Range Down and Luck Down pills to positive. This also restores health on pick up. It should be noted that this item can be replaced by the Lucky Foot, and is therefore unnecessary on Cain. However, PHD identifies pills after 5 seconds making it superior with respect to pills.

(Optional) 9 Volt: Speeds up the process by two charges.

(Optional) Safety Cap trinket: Increases the chance for pills to drop.

These three items together allow you to spawn a useful pill nearly every room, by the end of the game, one can expect to have 12 hearts, enough full heals to be able use them indiscriminately, and full speed, tears and range. If you have this combo you can focus on damage increasing items, and be more or less unstoppable.

In addition, if you come upon an arcade while having many hearts of health, you can use the blood donation machine and a full heal you probably have on hand in order to get an immense amount of coins. If you use those coins on a slot machine, you will probably break it and expose a dollar, and get a pretty fly or two to boot.

Note: Mom's Bottle of Pills only spawns one of six allotted pill types in one play-through, therefore the effectiveness of this stragegy is capped by the six random types the bottle can spawn.

Infinite Item Use Edit

This should probably be considered a cheat, and will ruin all the fun of the game.

If you have the X-Ray Vision and the battery, you can use your current item as many times as you wish. First, locate a room which has enemies, adjacent to the secret room. Leave at least one enemy alive. Wait in battle to get your 3 charges from the battery. With the x-ray specs, there will be a door open to the secret room, even though enemies are still alive; Leave to the secret room. When you go back to the original room, all the enemies will be respawned, and the max-3 counter on the battery will be reset. Repeat ad nauseum, using your item as many times as desired.

Good items to exploit include:

• The Book of Sin: keys, bombs, hearts, soul hearts, pills, money.
• The Book of Revelations: soul hearts
• Deck of Cards: some cards spawn beggars, slot machines, blood machines, keys, bombs, hearts, soul hearts, or money.
• Mom's Bottle of Pills: Gives the player a random pill upon use.
• Yum Heart: Gives the player one red heart upon use.
• Prayer Card: Gives the player a eternal heart upon use, which will be quickly converted into more max health.

Note: This can also be accomplished by exposing the secret room with bombs or any explosive items mid-battle. You can also use bombs on any door to open it for this purpose if you are fighting regular (non-boss) enemies.

Flight ItemsEdit

There are a few items in game that allow the player to fly over obstacles such as rocks, spikes, fires, blood (so you don't take damage) and pits. Here you will find a comparison of these items.

• The Bible: Activated item that transforms the player into a flying angel until he leaves the room. Instantly destroys Mom and Mom's Heart/It Lives upon use. Recharges in 6 rooms.
• A Pony: Increases speed by 2. When activated, charges across the room (recharges in 4 rooms). Also, the player is invincible while holding spacebar, and damages enemies who touch him; this can be used to defeat some enemies/bosses (such as Mom) without any risk of taking damage.
• The Pinking Shears: When activated, separates the player's head from his body, giving him flying until leaving the room. The severed body will chase and attack enemies, acting like a level 3/4 Meat Boy.However, it does more damage.
• Lord of the Pit: Gives the player flight and turns him into a demon (only visual effect).
• Transcendence: Gives the player flight and removes the lower part of his body (only visual effect). Functionally identical to Lord of the Pit.
• XII: The Hanged man: A tarot card that works just like Transcendence but wears off when he leaves the room.

Items added in the Wrath of the Lamb expansion:

• Dead Dove: Gives the player spectral tears (same as Ouija Board) and flight. With this combination the player can shoot tears at enemies from inside a rock and be invincible against grounded melee enemies.
• The Holy Grail: Gives the player flight and one empty heart container.
• Spirit of the Night: Same as Dead Dove.
• Fate: Grants flight and one eternal heart.
• White Pony: Increases speed by 2. Its activated ability makes you charge like A Pony and shoots beams of light like Crack the Sky. Also has the same invincibility trick as A Pony. (recharges in 6 rooms)