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Although burnout and low quality of life (QOL) are common among medical students, little remains known about personal fitness habits of medical students that may promote well-being.In 2012 the authors conducted a cross-sectional study of U.S. medical students to explore relationships between burnout, QOL, and compliance with Centers for Disease Control and Prevention (CDC) exercise recommendations. Wilcoxon-Mann-Whitney tests, Fisher exact tests, and multivariate logistic regression were performed.Among approximately 12,500 medical students invited to participate, 4,402 (35.2%) completed surveys. Most (2,738/4,367; 62.7%) engaged in aerobic exercise in accordance with CDC recommendations, while fewer (1,685/4,376; 38.5%) adhered to muscle strengthening recommendations. Burnout prevalence was lower among students who exercised aerobically consistent with CDC recommendations compared with those who exercised less (53.1% vs. 60.8%, P < .0001). Similarly, rates of burnout were also lower among students who strength trained consistent with CDC recommendations (51.8% vs. 58.6%, P < .0001). Overall QOL scores were higher for medical students adhering to CDC recommendations for aerobic exercise (7.2 vs. 6.6, P < .0001), strength training (7.2 vs. 6.8, P < .0001), or both aerobic and strength training (8.0 vs. 7.0, P < .0001). Compliance with CDC exercise guidelines remained independently associated with lower risk of burnout and higher QOL on multivariate analysis controlling for age, sex, relationship status, children, and year in school.Students whose aerobic exercise and/or strength training habits are consistent with CDC guidelines appear less likely to experience burnout and to have higher QOL.