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Abstract Background Burnout is common among physicians and has detrimental effects on patient care and physician health. Recent editorials call attention to perfectionism in medicine; however, no studies to date have examined the effect of perfectionism on burnout in physicians practicing in the United States. This study examined associations among demographics, perfectionism and personality traits, and burnout among practicing physicians. Methods This cross-sectional study included general pediatric and pediatric sub-specialist physicians. Out of the 152 physicians contacted, 69 enrolled (Meanage = 44.16 ± 9.98; 61% female). Emotional exhaustion, depersonalization, and personal accomplishment burnout were assessed via the Maslach Burnout Inventory. Validated instruments were used to measure personality and perfectionism. Data were analyzed using linear regression models. Results Across physicians assessed, 42% reported either high emotional exhaustion burnout or depersonalization burnout. High self-critical perfectionism uniquely predicted both high emotional exhaustion burnout (B = 0.55, 95%CI 0.25–0.85) and depersonalization burnout (B = 0.18, 95%CI 0.05–0.31). Low conscientiousness (B = -6.12; 95%CI, -10.95- -1.28) predicted higher emotional exhaustion burnout and low agreeableness (B = -3.20, 95%CI -5.93- -0.46) predicted higher depersonalization burnout. Conclusions Perfectionism is understudied among physicians and the current findings suggest that addressing system and individual-level factors that encourage perfectionism is warranted and may reduce risk for physician burnout.