Background: Women have historically had greater morbidity and mortality than men after conventional coronary artery bypass grafting (CABG) on cardiopulmonary bypass (ONCAB). It is controversial whether off-pump CABG (OPCAB) alters this gender-based disparity. Methods: The Society of Thoracic Surgeons National Cardiac Database was reviewed for risk factors and clinical outcomes of 42,477 consecutive, nonemergency, isolated, primary ONCAB or OPCAB cases performed at 63 North American centers that performed more than 100 OPCAB cases between January 1, 2004, and December 31, 2005. Odds ratios for adverse events, adjusted for 32 clinical and demographic covariates, were compared by multiple logistic regression models between women and men who had OPCAB versus ONCAB. All analyses were by intention-to-treat; 355 (2.2%) patients converted from OPCAB to ONCAB intraoperatively were included in the OPCAB group. Results: Women (n = 11,785) and those treated with OPCAB (n = 16,245) were older and had more comorbidities than men (n = 30,662) and those treated with conventional ONCAB (n = 26,202). Overall, adjusted odds ratios for death and most major complications in both men and women were significantly lower with OPCAB than with ONCAB. Among ONCAB cases only, women had a significantly greater adjusted risk of death, prolonged ventilation, and long length of stay than men. In contrast, among OPCAB cases, women had lower risk of reexploration than men and similar risks for death, myocardial infarction, and prolonged ventilation and hospital stay. Conclusions: OPCAB is associated with lower adjusted risk of death and major adverse events than ONCAB. OPCAB benefits both men and women and reduces the gender disparity in clinical outcomes after CABG.