If it is unlocked, The Lost starts with this item along with spectral tears and flight. Using it will reroll Holy Mantle.
The Lost no longer starts with the D4. If used however, it will no longer reroll their Holy Mantle.
Every Cube of Meat produced using Potato Peeler count as an item for rerolling to the D4. Because health usually is not removed in rerolling items this is useful to increase the number of items at the expense of the item pool.
Multiple copies of the same item (as generated by Diplopia, the Debug Console, or gathering them from multiple item pools (e.g. Steam Sale from both the Shop and Greed) will each be rerolled into a different item, even though the duplicates are not present on the pause screen.
There is a small chance that D4 will not reroll every item: the game makes a number of attempts to reroll each item, but if they all fail to produce a new item that is available and applicable, the original remains unchanged.
If used while playing as Jacob and Esau, it will only reroll the items on the character that used it.
Book of Virtues: Removes all of Isaac's wisps and gives him one random wisp for every two items rerolled. Book of Virtues will not be rerolled in the process.
The image of the D4 that appears on activation is incorrect; it shows the numbers 9, 7, and 8 on the right face of the die, when it should depict numbers consistent with the left face (i.e. 1 at the top, 3 at the front, and 4 at the right).
3DS The icon of D4 as seen on the lower 3DS screen.
Previously held items are not removed from the pause menu, which makes it difficult to determine which items Isaac currently has.
When D4 is used with a co-op baby present, the baby's sprite will turn into a glitched sprite of Isaac.
If Tech.5 is fired while D4 is used, the laser will appear to continue firing for the rest of the room.
If Isaac rerolls Schoolbag, he will keep both active items, but if he picks up a new active item it will swap with the one currently selected and the other will disappear.
When Schoolbag is rerolled away while another active item is held along D4, the other active item will be dropped on a pedestal. Activating D4 after the other active item is dropped will then reroll D4 itself.
The way the originating pools for items are tracked is bugged in two ways, making it possible for items to reroll into different pools.
An item picked up is assigned the pool of the most recently generated item; usually this has correct results but a difference can be seen, for instance, by killing a boss, entering a Devil Deal that has items and collecting the boss reward after seeing the Devil items. The boss item will be rerolled to a Devil pool item with D4.
Items that are rerolled are assigned the pool of the item with the highest item ID. This means one reroll with the D4 will probably go as expected, but further rerolls will be proliferated by items from the pool that had the highest ID before the first reroll.
If Isaac has the shield granted by Holy Card, he will lose it upon activating the D4.