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To describe educational outcomes for a national cohort of students who enrolled in MD–PhD programs at medical school matriculation (MD–PhD matriculants).The authors used multivariate logistic regression to identify factors independently associated with overall MD–PhD program attrition (MD-only graduation or medical school withdrawal/dismissal) compared with MD–PhD program graduation among the 1995–2000 national cohort of MD–PhD matriculants at medical schools with and without Medical Scientist Training Program (MSTP) support.Of 2,582 MD–PhD matriculants, 1,885 (73.0%) were MD–PhD graduates, 597 (23.1%) were MD-only graduates, and 100 (3.9%) withdrew/were dismissed from medical school by July 2011. MD–PhD matriculants at non-MSTP-funded schools (adjusted odds ratio [AOR], 1.96; 95% confidence interval [CI], 1.60–2.41) and who had lower Medical College Admission Test scores (< 31 versus ≥ 36: AOR, 1.60; 95% CI, 1.20–2.14; 31–33 versus ≥ 36: AOR, 1.31; 95% CI, 1.01–1.70) were more likely to leave the MD–PhD program; matriculants who reported greater planned career involvement in research (AOR, 0.65; 95% CI, 0.51–0.84) and matriculated more recently (AOR, 0.90; 95% CI, 0.85–0.96) were less likely to leave the MD–PhD program. Gender, race/ethnicity, and premedical debt were not independently associated with overall MD–PhD program attrition.Most MD–PhD matriculants completed the MD–PhD program; most of those who left were MD-only graduates. Findings regarding variables associated with attrition can inform efforts to recruit and support students through successful completion of MD–PhD program requirements.