The periprocedural management, bleeding risks, and outcomes of patients taking warfarin previous to percutaneous coronary intervention (PCI) have not been well characterized. All patients undergoing PCI in the National Cardiovascular Data Registry from January 1, 2004 to March 31, 2006 were analyzed (n = 307,443). Multivariable modeling was used to evaluate the association between home warfarin use and in-hospital mortality and bleeding (requiring blood transfusion and/or prolonging hospital stay and/or causing hemoglobin drop >3.0 g/dl). Patients undergoing elective PCI and urgent PCI (primary/rescue/facilitated PCI with symptoms fewer than 24 hours) were analyzed separately. Overall, 11,173 patients (3.6%) were taking warfarin previous to PCI. Compared with patients not taking warfarin, patients taking warfarin were older and had greater burden of comorbidities. Patients taking warfarin were less likely to receive aspirin, theinopyridines, and glycoprotein IIb-IIIa antagonists during PCI. Unadjusted bleeding rates (elective PCI = 3.2% vs 1.9%; urgent PCI = 8.2% vs 4.8%) and in-hospital mortality (elective PCI = 1.4% vs. 0.6%; urgent PCI = 8.6% vs. 4.5%) were higher among patients taking warfarin. After adjustment for clinical characteristics, the risk of in-hospital mortality was similar with and without previous warfarin use. However, the adjusted risk of bleeding was significantly higher in patients receiving warfarin, for both elective (odds ratio = 1.26, 95% confidence interval = 1.09 to 1.46) and urgent PCI (odds ratio = 1.42, 95% confidence interval = 1.14 to 1.76). In conclusion, while fewer than 5% of patients undergoing PCI are taking previous warfarin, these patients have a higher risk of in-hospital bleeding events but a similar risk of mortality despite lower use of antiplatelet agents.