The relationship between increasing numbers and diversity of medical school enrollees and the US physician workforce size and composition has not been described. To identify demographic and prematriculation factors associated with medical school matriculants' outcomes. Retrospective study using deidentified data for the 1994-1999 national cohort of 97,445 matriculants who were followed up through March 2, 2009, and had graduated, had withdrawn, or were dismissed. Data were analyzed using multivariable logistic regression to identify factors associated with suboptimal outcomes. Academic withdrawal or dismissal, nonacademic withdrawal or dismissal, and graduation without first-attempt passing scores on the US Medical Licensing Examination Step 1 and/or Step 2 Clinical Knowledge (CK) compared with graduation with first-attempt passing scores on both of the examinations. Of 84,018 matriculants (86.2%), 74,494 graduated and had first-attempt passing scores on both the Step 1 and Step 2 CK (88.7%), 6743 graduated and did not have first-attempt passing scores on the Step 1 and/or Step 2 CK (8.0%), 1049 withdrew or were dismissed for academic reasons (1.2%), and 1732 withdrew or were dismissed for nonacademic reasons (2.1%). Variables associated with greater likelihood of graduation without first-attempt passing scores on the Step 1 and/or Step 2 CK and of academic withdrawal or dismissal, respectively, were (1) Medical College Admission Test scores (scores of 18-20 [2.9% of sample] vs > 29: adjusted odds ratio [AOR], 13.06 [95% confidence interval {CI}, 11.56-14.76] and AOR, 11.08 [95% CI, 8.50-14.45]; scores of 21-23 [5.6% of sample] vs > 29: AOR, 7.52 [95% CI, 6.79-8.33] and AOR, 5.97 [95% CI, 4.68-7.62]; and scores of 24-26 [13.9% of sample] vs > 29: AOR, 4.27 [95% CI, 3.92-4.65] and AOR, 3.56 [95% CI, 2.88-4.40]), (2) race/ethnicity (Asian or Pacific Islander [18.2% of sample] vs white: AOR, 2.15 [95% CI, 2.00-2.32] and AOR, 1.69 [95% CI, 1.37-2.09]; underrepresented minority [14.9% of sample] vs white: AOR, 2.30 [95% CI, 2.13-2.48] and AOR, 2.96 [95% CI, 2.48-3.54]), and (3) premedical debt (> or = $50,000 [1.0% of sample] vs no debt: AOR, 1.68 [95% CI, 1.35-2.08] and AOR, 2.33 [95% CI, 1.57-3.46]). Lower scores on the Medical College Admission Test, nonwhite race/ethnicity, and premedical debt of at least $50,000 were independently associated with a greater likelihood of academic withdrawal or dismissal and graduation without first-attempt passing scores on the US Medical Licensing Examination Step l and/or Step 2 CK.