Gender-based outcomes have not been evaluated in unselected patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). We investigated whether gender influences the relative safety and efficacy of DESs compared with bare metal stents (BMSs) in routine clinical practice. Using the National Heart, Lung, and Blood Institute Dynamic Registry, in-hospital and 1-year outcomes were stratified by gender in patients who received ≥1 DES (486 women, 974 men) or BMS (631 women, 1,132 men). There were significant baseline differences by gender, including older age and a higher prevalence of co-morbidities in women and more previous coronary artery disease in men. There were no gender-related differences in in-hospital myocardial infarction, coronary artery bypass grafting, and death in those treated with BMSs or DESs. Antiplatelet use and stent thrombosis (1.3% of women vs 1.2% of men, p = 0.85) were similar at 1 year with DESs. At 1 year, patients with DESs had a lower rate of repeat PCI (14.1% in women vs 9.5%, p = 0.02; 12.0% in men vs 8.8%, p = 0.02). Adjusted 1-year outcomes in patients with BMSs and DESs, including death and myocardial infarction, were independent of gender. Use of DESs was the only factor, other than age, that conferred a lower risk for the need for repeat PCI in women (relative risk 0.61, 95% confidence interval 0.41 to 0.89, p = 0.01) and men (relative risk 0.68, 95% confidence interval 0.51 to 0.91, p = 0.001). In conclusion, the widespread use of DESs is safe and has decreased clinically driven revascularization compared with BMSs equally in women and men.