Note that Missing No. can be re-rolled into, but can't be re-rolled out of.
The D4 does not remove traits or abilities inherent to a character, i.e. Azazel's Brimstone-like attack, Lilith's Incubus or The Forgotten's bone attack.
Starting items from Challenges will also not be rerolled
Items that grant pickups (like Pyro or A Dollar) do not remove their bonuses when rerolled.
The D4 can grant items that have not yet been unlocked.
The items gained by the D4 count towards the collection page.
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.
Smelted/Swallowed trinkets (via Marbles, Smelter or Gulp!) will not be rerolled.
Items rerolled away from Isaac do not return to circulation and can't be encountered again.
Items rerolled away are returned to circulation and can be encountered again later in the run.
D4 doesn't remove transformation progress, meaning that he will keep a transformation or gain one if he gets a transformation item while having two points of this transformation before rerolling.
D4 removes transformation progress.
If it is unlocked, The Lost starts with this item along with spectral tears and flight. Using it will reroll Holy Mantle.
The D4 does not give hearts that would be otherwise gained from item pickups, but will remove previously collected health upgrade items.
If used while playing as Jacob and Esau or Tainted Lazarus, it will only reroll the items on the character that used it.
Tainted Isaac can avoid having their health subtracted form re-rolling health up items by dropping health items for full inventory before rerolling.
D4's quality is treated as 2 for the purposes of Bag of Crafting.
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.
Interactions
Car Battery: Instantly re-rolls Isaac's items twice, which doubles the speed at which the item pools are exhausted and transformations are achieved.
Potato Peeler: Every Cube of Meat produced counts as an item available to reroll. Because health usually is not removed when using the D4, this is useful to increase the number of items at the expense of the item pool.
3DS The icon of D4 as seen on the lower 3DS screen.
D4's splash image which appears when it's activated.
Trivia
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).
Bugs
Bug!
Previously held items are not removed from the pause menu, which makes it difficult to determine which items Isaac currently has if they're too many to appear on the HUD.
Bug!
When D4 is used with a co-op baby present, the baby's sprite will turn into a glitched sprite of Isaac.
Bug!
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.
Bug!
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.
Bug!
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 with no item pool (starting items, fixed drops etc.) will always use the item pool of the most recently generated item from an item pool as a result; if no items from item pools were encountered yet, the treasure room pool is used.
Bug!
If Isaac uses D4 in a room with an item before taking it, that item is assigned the pool of the most recently collected item. For example, if Isaac takes a Devil item, then uses D4 in a Treasure Room with an item before taking it, the latter will reroll into Devil items on subsequent uses of D4.
Bug!
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.