This nationally representative study sought to identify personality traits that are associated with academic achievement in medical school. Third-year medical students, who completed an initial questionnaire in January 2011, were mailed a second questionnaire several months later during their fourth year. Controlling for sociodemographic characteristics and burnout, the authors used multivariate logistic regressions to determine whether Big Five personality traits were associated with receiving honors/highest grade in clinical clerkships, failing a course or rotation, and being selected for the Alpha Omega Alpha or Gold Humanism Honor Society. The adjusted response rates for the two surveys were 61 (n=564/919) and 84% (n=474/564). The personality trait conscientiousness predicted obtaining honors/highest grade in all clinical clerkships. In contrast, students high in neuroticism were less likely to do well in most specialties. Students with higher conscientiousness were more likely to be inducted into the Alpha Omega Alpha Honor Society, while students high in openness or agreeableness traits were more likely to be inducted into the Gold Humanism Honor Society. Burnout was not associated with any clinical performance measures. This study suggests the importance of personality traits, particularly conscientiousness, in predicting success during the clinical years of medical school. Medical educators should consider a nuanced examination of personality traits and other non-cognitive factors, particularly for psychiatry.