Purpose Educational outcomes for a national cohort of MD-PhD program matriculants have not been described. Method The authors used multivariate logistic regression to identify factors independently associated with overall MD-PhD program non-completion (both MD-only graduation and medical-school withdrawal/dismissal) compared with MD-PhD program graduation among the 1995–2000 national cohort of MD-PhD program enrollees at matriculation at medical schools with and without National Institutes of Health Medical Scientist Training Program (MSTP) support. Results Of 2,582 MD-PhD program enrollees in this national cohort (1,729[67.0%] men; 853[33.0%] women), 1,885 (73.0%) were MD-PhD-program graduates, 597 (23.1%) were MD-only graduates, and 100 (3.9%) withdrew/were dismissed from medical school. Enrollees at non-MSTP-funded schools compared with 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 (MCAT) scores (<31 vs. ≥36: AOR, 1.60; 95% CI, 1.20–2.14; 31–33 vs. ≥36: AOR, 1.31; 95% CI, 1.01–1.70)were more likely to have left the MD-PhD program; enrollees who reported greater planned career involvement in research (AOR, 0.65; 95% CI, 0.51–0.84) and matriculated in more recent years (AOR,0.90; 95% CI, 0.85–0.96) were less likely to have left the MD-PhD program. Gender, race/ethnicity, and pre-medical debt were not independently associated with overall MD-PhD program non-completion. Conclusions Most MD-PhD matriculants completed the MD-PhD program, and 85.7% (597/697) of non-completers graduated from medical school. The authors’ findings regarding variables associated with MD-PhD program attrition can inform efforts to recruit and support MD-PhD program enrollees through successful completion of the dual-degree program.