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This study investigated the effect of medical students’ self-reported grit, empathy, and self-directed learning on their well-being. These measures were administered as part of a larger battery of measures at multiple timepoints during medical school. The study participants are M4s and M3s at Hackensack Meridian School of Medicine. Grit was shown to predict significantly lower levels of reporting mental distress for students at follow-up, while self-directed learning and empathy were not significantly related to later well-being. This result adds to a growing body of literature that grit is an important trait to measure and track in medical education, as it may serve to protect against development of burnout and mental distress in medical school.