PURPOSE: To describe educational outcomes for a national cohort of students who enrolled in MD-PhD programs at medical school matriculation (MD-PhD matriculants). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.