OBJECTIVE The primary objective of this study is the compare the association between bleeding and the use unfractionated heparin (UFH) versus bivalirudin during percutaneous coronary intervention (PCI). BACKGROUND In patients undergoing PCI, the risk of bleeding with use of bivalirudin compared with UFH in the absence of glycoprotein IIb/IIIa inhibitors is not well defined. METHODS Patients undergoing PCI with either UFH or bivalirudin monotherapy at a single institution between 2007 and 2014 were included (n = 6,143). Propensity score matching was used to adjust for baseline characteristics yielding 2,984 well matched patients (1,492 in each group). The primary endpoint was major non-coronary artery bypass graft (non-CABG) related bleeding as defined by a Bleeding Academic Consortium type 3 or 5. Secondary outcomes included combined major and minor bleeding, in-hospital death, periprocedural myocardial infarction, and recurrent ischemia requiring urgent revascularization (repeat PCI). RESULTS In the propensity matched cohort, there was no difference in major bleeding between UFH and bivalirudin monotherapy (1.8% versus 2.4%, P = 0.305). Combined major and minor bleeding was also similar between the two groups (4.3% versus 4.3%, P = 1.0). Likewise, no differences were observed between the bivalirudin and UFH groups in terms of in-hospital death (0.4% versus 0.5%, P = 0.592), periprocedural myocardial infarction (1.5% versus 2.0%, P = 0.332) and repeat PCI (0.7% versus 0.8%, P = 0.669). CONCLUSIONS Among patients undergoing PCI, there was no significant difference in rate of bleeding between bivalirudin and heparin monotherapy in a real-world setting.