Daydream
- Enemies only have 75% of their health
- Gibbing enemies is easier
- No matter which kind of damage you encounter, you always lose 1 HP only
- On pick up, you will receive twice as much ammo
- Your health is restored at checkpoints
- The Guardian (in "Ruins") is easier to beat
- Tarot cards are not available
- Level "Prison" is not available
- Level "Abandonded Factory" is not available
- Level "Forest" is not available
Insomnia
- You only receive half the damage
- On pick up, you receive 50% more ammo
- Your health is restored at checkpoints
- Level "Prison" is not available
- Level "Forest" is not available
Nightmare
- Console cheats are disabled
- Level "Forest" is not available
Trauma
- Enemies don't leave souls
- Quicksaves are disabled
- Console cheats are disabled
- You receive 50% more damage
- Chapter 5 is not available
Completing the first game on Trauma also results in an alternate ending, though it is not recognized as canon by neither Battle Out of Hell, nor any of the sequels.
Completing Battle Out of Hell on Trauma unlocks a hidden bonus level featuring the portraits (and souls) of Painkiller's original developers - People Can Fly.
