ABSTRACT: OBJECTIVE:To evaluate physician burnout, well-being, and work unit safety grades in relationship to perceived major medical errors. PARTICIPANTS AND METHODS:From August 28, 2014, to October 6, 2014, we conducted a population-based survey of US physicians in active practice regarding burnout, fatigue, suicidal ideation, work unit safety grade, and recent medical errors. Multivariate logistic regression and mixed-effects hierarchical models evaluated the associations among burnout, well-being measures, work unit safety grades, and medical errors. RESULTS:Of 6695 responding physicians in active practice, 6586 provided information on the areas of interest: 3574 (54.3%) reported symptoms of burnout, 2163 (32.8%) reported excessive fatigue, and 427 (6.5%) reported recent suicidal ideation, with 255 of 6563 (3.9%) reporting a poor or failing patient safety grade in their primary work area and 691 of 6586 (10.5%) reporting a major medical error in the prior 3 months. Physicians reporting errors were more likely to have symptoms of burnout (77.6% vs 51.5%; P<.001), fatigue (46.6% vs 31.2%; P<.001), and recent suicidal ideation (12.7% vs 5.8%; P<.001). In multivariate modeling, perceived errors were independently more likely to be reported by physicians with burnout (odds ratio [OR], 2.22; 95% CI, 1.79-2.76) or fatigue (OR, 1.38; 95% CI, 1.15-1.65) and those with incrementally worse work unit safety grades (OR, 1.70; 95% CI, 1.36-2.12; OR, 1.92; 95% CI, 1.48-2.49; OR, 3.12; 95% CI, 2.13-4.58; and OR, 4.37; 95% CI, 2.06-9.28 for grades of B, C, D, and F, respectively), adjusted for demographic and clinical characteristics. CONCLUSION:In this large national study, physician burnout, fatigue, and work unit safety grades were independently associated with major medical errors. Interventions to reduce rates of medical errors must address both physician well-being and work unit safety.