When Isaac takes damage, there is a chance that a Soul Heart may spawn.
Monsters have a chance to drop a Half Red Heart after being killed. Chance depends on killed monster's base health.
Notes
This item has a 1% chance to drop when defeating Sisters Vis.
The chance for Gimpy to spawn a Soul Heart depends on the luck stat, and the formula used to determine the chance is:
At base luck (0), the chance is 10%, maxing out at 50% at 20 luck.
The chance for Gimpy to spawn a Soul Heart depends on the luck stat and is based on this formula:
This means that the chance starts at 8% at 0 luck, minimizes at 0% at -4 luck, and maximizes at 100% at 46 luck.
Monsters that have less than 10 HP have a 1% chance to drop a Half Red Heart.
Monsters that have 10 to 29 HP have a 5% chance to drop a Half Red Heart.
Monsters that have more than 30 HP have a 10% chance to drop a Half Red Heart.
Synergies
Blood Oath: For each half heart damaged by Blood Oath, Gimpy has a chance to drop a soul heart. Synergy further improves with luck.
Dark Bum: Dark Bum can collect the Half Red Hearts that enemies drop, which when combined with the chance to drop Soul Hearts when damaged, is a good way to generate Soul and Black Hearts as well as other pickups.
Interactions
Ace Cards: Enemies that are turned into pickups can't drop hearts.
E. Coli/Flush!: Enemies that are turned into poop can't drop hearts.