Is it wise to try unrecognized pills that I find?

Solution 1:

TL;DR: Yes, try every pill you find

In the game, according to the list near the bottom of the items page on the wiki, there are

8 pills with definitely good effects:

1. Bad Gas: poisons surrounding enemies
2. Balls of Steel: gives 2 soul hearts
3. Full Health
4. Health Up
5. Pretty Fly: adds a close orbiting fly
6. Range Up
7. Speed Up
8. Tears Up

4 pills with definitely bad effects:

1. Health Down
2. Range Down
3. Speed Down
4. Tears Down

And 5 pills with neutral effect or possibly good or bad effect:

1. Bad Trip: Take 1 damage if more than 1 heart left, otherwise grants full health
2. Bombs Are Key: Swaps bomb and key counts
3. Explosive Diarrhea!: Drops lit bombs while walking for a short time
4. I Found Pills: no important effect
5. Telepills: Teleport to a random room

If we assume that the set of pills for each playthrough is uniformly chosen from all of the pills, then it would be wise to take every unidentified pill because it is more likely to be good than bad, and even some of the neutral pills can be useful in the right circumstances.

If we assume a reasonable bad distribution, with 2 bad pills, 2 neutral pills, and 2 good pills (generally worse than random but possibly what actually happens), it may still be wise to take random pills. Some of the neutral pills have useful effects at times, so it would be best to try random pills with as many of the following conditions as possible

• You have 1 health (so Bad Trip heals you)
• You want to switch bombs and keys, or at least wouldn't care if they switch (Bombs are Key)
• You want to drop bombs in the room, possibly to break rocks or look for the secret room (Explosive Diarrhea!)
• You would be OK teleporting into any room in the level (Telepills)

So the absolute best time to test pills would be when you have defeated the boss and cleared the level and you have 1 heart and you still need to break a rock somewhere.

However, even discounting the possible benefit of neutral pills, I would say it is still good to test every pill because knowing what pill you have and what pills there are can be useful. If you know that you have an Explosive Diarrhea! pill for example, you can use it against a boss or a room full of enemies that are easier to kill with bombs.

Also, if you know what bad pills there are, you can more accurately determine whether to buy the PhD or Lucky Foot, because they transform bad pills into the corresponding good ones. So if the bad pills are Range Down and Speed Down, and you already have both of those at max, it is probably not worth it to buy the PhD because you will not get any new benefit from those previously bad pills.

Thus I conclude that unless we know that we can get very bad sets of pills, it is probably good to try unidentified pills.

Solution 2:

"???" Pills should always be taken, but there are some moments that are better than others.

If your character has one or less heart containers, the Health Down result will always be Health Up instead.

One note about Health Up pills: gaining an empty heart container counts as red heart damage for the floor, and will drop your chances of a Satan/Angel room spawning after the boss. Use them after you kill the boss of the floor, unless it's Mom's Heart, Satan, Isaac, or ??? which don't give Satan/Angel rooms.

Telepills can send you to the I Am Error room or Satan/Angel rooms prematurely, or remove you from a Curse room when you've not collected other items inside (pills are one of the spawns from red chests), so be cautious about taking pills before you clear a floor, if you haven't identified telepills yet. If you are going to buy an item from the Satan room (once it has opened), and you have one or less heart containers, you can risk a ??? pill in hopes for a Health Up, but may also roll telepills if they're not identified yet, which may cause you to miss the chance to buy Satan items.

In general, if you find an unidentified pill, keep it until another Q key item shows up, then test it after you defeat the floor's boss. If you don't find a replacement item, hold onto the pill until you can obtain Lucky Foot or Ph.D, which either prevent or retroactively convert stat down pills to stat ups, respectively.

Lastly, Cain starts with Lucky Foot, so Pills will never have stat-down effects when playing him. He is an especially good character when using Mom's Pill Bottle, as a result.