Objectives: This study evaluated differences in outcome among women and men enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Background: Women and men with coronary artery disease have different clinical presentations and outcomes that might be due to differences in management. Methods: We compared baseline variables, study interventions, and outcomes between women and men enrolled in the BARI 2D trial and randomized to aggressive medical therapy alone or aggressive medical therapy with prompt revascularization. Results: At enrollment, women were more likely than men to have angina (67% vs. 58%, p < 0.01) despite less disease on angiography (Myocardial Jeopardy Index 41 ± 24 vs. 46 ± 24, p < 0.01; number of significant lesions 2.3 ± 1.7 vs. 2.8 ± 1.8, p < 0.01). Over 5 years, no sex differences were observed in BARI 2D study outcomes after adjustment for difference in baseline variables (death/myocardial infarction/cerebrovascular accident: hazard ratio: 1.11, 99% confidence interval [CI]: 0.85 to 1.44). However, women reported more angina than men (adjusted odds ratio: 1.51, 99% CI: 1.21 to 1.89, p < 0.0001) and had lower scores for the Duke Activity Status Index (adjusted beta coefficient: -1.58, 99% CI: -2.84 to -0.32, p < 0.01). Conclusions: There were no sex differences in death, myocardial infarction, or cerebrovascular accident among patients enrolled in the BARI 2D trial. However, compared with men, women had more symptoms and less anatomic disease at baseline, with persistence of higher angina rates and lower DASI scores after 5 years of medical therapy with or without prompt revascularization. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305) © 2013 American College of Cardiology Foundation.