More than 1.2 million percutaneous coronary intervention (PCI) procedures are performed each year in the United States, with average hospital costs of more than 10,000 per procedure. Despite ongoing improvements in device technology and adjunct pharmacology, both ischemic complications (eg, periprocedural myocardial infarction) and bleeding complications remain relatively common and are associated with both increased costs (in the short term) and mortality (in the longer term). Recently, the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 clinical trial demonstrated that the use of the direct thrombin inhibitor, bivalirudin, with provisional glycoprotein (GP) IIb/IIIa inhibitor for selected patients in place of a conventional anticoagulation strategy of heparin and routine use of a GP IIb/IIIa inhibitor, resulted in comparable rates of ischemic complications and a significant reduction in the frequency of both major and minor bleeding complications. A prospectively designed economic analysis was performed using data from 4651 US patients who participated in REPLACE-2. In this analysis, patients who were assigned to the bivalirudin and provisional GP IIb/IIIa inhibitor strategy had anticoagulation costs during PCI that were approximately 400 per patient lower than those with heparin plus routine GP IIb/IIIa inhibition. Bivalirudin also produced corresponding decreases in total in-hospital costs and aggregate 30-day medical care costs. These cost savings derived both from the lower acquisition cost of the antithrombotic therapy and the reduced rate of bleeding complications, which accounted for approximately 20% of the cost offsets. These results suggest that for patients similar to those studied in REPLACE-2 (ie, low to moderate risk PCI procedures), use of bivalirudin and provisional GP IIb/IIIa inhibition compared with heparin and routine GP IIb/IIIa inhibition can result in similar rates of ischemic complications, reduced bleeding, and substantial cost savings to both hospitals and the healthcare system. Whether these benefits can be extended to higher risk patient subsets including patients with non-ST elevation or ST elevation myocardial infarction is currently under investigation.