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Objective: Approximately half of all U.S. medical students are experiencing burnout. A previous study has demonstrated that higher levels of spirituality are associated with less burnout in medical students, yet no studies have examined the relationship between religious affiliation and burnout in medical students. The purpose of this study is to determine if specific religious affiliation and level of religious involvement is associated with less burnout in medical students., Methods: A cross-sectional online survey was sent to all students attending five different osteopathic and allopathic medical schools in Kansas and Missouri. It contained a validated burnout measure, an item to identify religious affiliation, and items to quantify religious involvement., Results: A response rate of 11.5% (495/4,300) was obtained. An ANOVA showed religious affiliations and burnout scores did not have any statistically significant relationships (F = 0.762, P = 0.619). Additionally, identification as an active participant within a religious affiliation had a statistically significant effect on burnout scores (F = 7.793, P = 0.005)., Conclusions: This is the first study within the U.S. to show that religious affiliation is not associated with medical student burnout and that medical students who consider themselves to be active participants of their religion may be at lower risk of developing burnout, regardless of the faith they practice., (Copyright 2021 by the Missouri State Medical Association.)