Women constitute a high-risk population for bleeding, which is a major prognostic predictor after percutaneous coronary catheterization procedures. We prospectively followed 3,261 consecutive percutaneous coronary procedures performed by radial artery catheterization (RAC) or femoral artery catheterization (FAC). The primary study objective was to determine the relative incidences of in-hospital major and minor puncture-related hemorrhages. Secondary objectives were to (1) identify predictors of major bleeds and (2) estimate how often a second, alternative access site is required for catheterization. In women, no major bleeding occurred after 299 RAC procedures performed, whereas 25 major bleeding episodes occurred after 601 FAC procedures (p = 0.0008). Women who underwent RAC also had a significantly lower incidence of minor hemorrhages than women who underwent FAC (19 of 299, 6.4%, vs 237 of 601, 39.4%, respectively, p = 0.00001). On multivariate analysis, independent predictors of major bleeding were FAC (odds ratio [OR] 27.4, 95% confidence interval [CI] 3.8 to 199.9), use of glycoprotein IIb/IIIa inhibitors (OR 5.6, 95% CI 2.7 to 11.9), female gender (OR 4.5, 95% CI 2.2 to 9.0), age >70 years (OR 2.4, 95% CI 1.2 to 4.8), and an acute coronary syndrome setting (OR 2.4, 95% CI 1.1 to 5.0). Women who underwent RAC were more likely to require a second access site than men (14% vs 1.7%), but operators less selective in RAC use successfully completed the procedure by radial approach in >90% of patients. In conclusion, extensive RAC was more effective at preventing access-related bleeding complications in women than FAC.