Background: Early studies suggested that morbidity and mortality after percutaneous coronary intervention (PCI) were greater for women than men. However, in recent reports, sex-related differences in short-term outcome have decreased as outcomes among women have improved. Objective: The aim of the study was to evaluate the effect of sex on long-term mortality among a large cohort of patients undergoing PCI in the contemporary era. Methods: Three hospitals in New York City contributed prospectively defined data elements on 4284 consecutive patients undergoing PCI in 1998 to 1999. All-cause mortality at a mean follow-up of 3 years was the primary end point. Results: Of the 4284 patients, 1331 (31%) were women. Women were significantly older than men (mean age 67 vs 62 years, P < .001) and less often white (72% vs 80%, P < .001). Hypertension (78% vs 66%, P < .001) and diabetes (36% vs 22%, P < .001) were more prevalent in women. Prior cardiac surgery (14% vs 19%, P = .001) and previous myocardial infarction (MI) (33% vs 36%, P = .08) were less common among women. Presentation with unstable angina was more frequent in women (45% vs 41%, P = .034), whereas presentation with acute MI did not differ by sex. Congestive heart failure developed more commonly among women (7.1% vs 4.1%, P < .001). The extent of coronary disease (1-, 2-, or 3-vessel disease) did not differ between women and men. Mean ejection fraction was 52% in women and 50% in men (P < .001). Stents were placed in 77% of both groups. Procedural success was 97% for both women and men. Inhospital adverse outcomes including death, post-PCI MI, emergency bypass surgery, abrupt closure, and stent thrombosis were uncommon and not different between groups. Mortality at 3 years was 10% for women and 8.9% for men (P = .197). However, using Cox proportional hazards analysis to adjust for comorbidities and possible confounders, female sex was associated with a significant independent reduction in the hazard of long-term mortality (hazard ratio 0.78, 95% CI 0.620-0.969, P = .02). Conclusions: Despite more high-risk characteristics, female sex conferred a long-term survival advantage after PCI.