Background-Women are at a higher risk for bleeding/vascular complications (VC) related to cardiovascular procedures. Although the overall incidence of percutaneous coronary intervention (PCI)-related bleeding/VC has declined, the impact of this decline, specifically in women, is unknown.Methods and Results-We studied 13 653 female and 32 334 male consecutive cases, from 2002 to 2007, in the Northern New England PCI Registry. We sought to (1) compare absolute rates of bleeding/VC in women and men over time, (2) define predictors of bleeding/VC in women and men undergoing PCI, and (3) trend the impact of female gender in predicting bleeding/VC over time. Bleeding/VC was defined as any access-site vessel injury requiring surgical intervention or bleeding requiring transfusion. The overall risk of bleeding/VC was significantly higher in women versus men (4.5 +/- 1.3% versus 1.6 +/- 0.5%; P < 0.004). Over time, there was a significant (P < 0.001) 50% decrease in absolute bleeding/VC rates in both women and men. After adjustment for baseline differences, female gender remained a significant predictor of increased risk in 2007 (odds ratio, 2.6; 95% CI, 1.74 to 3.91). Independent predictors of increased risk of bleeding/VC in women included older age, shock, renal failure, presentation with non-ST-elevation myocardial infraction and larger sheath sizes, whereas the use of fluoroscopy-guided access, closure devices, history of dyslipidemia or prior PCI, and use of bivalirudin were protective.Conclusion-Women undergoing PCI have had a significant decline in bleeding/VC rates during the last 6 years. Despite the improvement in procedural safety, female gender continues to be associated with a > 2-fold risk of bleeding/VC compared with men. (Circ Cardiovasc Intervent. 2009;2:423-429.)