Upon activation all pickups in the room (bombs, coins, hearts, keys, pills, tarot cards, trinkets, and chests) will randomly change into another pickup item, even un-detonated troll bombs. The D20 can even help in combat as it will turn War's troll bombs into many pick-ups.
- Any item able to spawn a sufficient amount of pickups to transform, such as Pageant Boy or the IV Bag.
- The Habit can be used to abuse the Blood Donation Machine inside Arcade rooms along with the D20 to re-roll large amounts of coins and other potentially unwanted items. With a sufficient number of pickups on the screen enough hearts should be created to make up any lost health, and pickups re-rolled into chests can dramatically increase the number of available pickups to re-roll.
- The D20 is also effective if used quickly with the bombs from the Anarchist's Cookbook or XVI The Tower, as they are also changed into other pickups.
- There is a hard limit of pickups that the D20 will re-roll in a single use (around 30).
- If D20 is used right after a coin is collected, the coin (with disappearing animation) will be also rerolled, so you can get both.
- Unlike the D6, the D20 cannot re-roll pickups that are for sale at the shop unless they have already been purchased without being picked up.
- The D20 is sometimes able to re-roll the remains of opened Chests, though only if any Collectable Items inside have been removed. This effect will not always work for unknown reasons.
- If Bum Friend is moving towards a coin and you reroll it with the D20, Bum Friend will disappear for that room.
- The D20 can be used inside Curse Rooms to spawn red chests at a higher frequency.
- Re Rolling lots of pickups over and over again in the same room (through the use of items such as the Habit and Scapular) will eventually cause the game to crash.
- This item is most likely be a reference to Dungeons & Dragons, a popular tabletop role-playing game which uses a 20-sided die.