The economics of bleeding complications and the role of antithrombotic therapies in percutaneous coronary intervention (PCI) are discussed. More than 1 million PCI procedures are performed annually in the United States, at a mean cost of hospitalization of approximately $9,000 and billions of dollars in total health care costs. Ischemic complications have been reduced to the point that bleeding has become the most common complication. Bleeding complications and transfusions are also among the most costly complications in PCI, accounting for an incremental cost of hospitalization after PCI that may exceed $10,000, due to increased length of stay and the use of additional resources such as ultrasound evaluation and surgical repair of the vascular site. Anemia and transfusions are also associated with increased morbidity and mortality, contributing to additional treatment costs beyond those directly attributable to correcting the bleeding complication. In the past decade, significant reductions in heparin dose and warfarin use were associated with reduced bleeding complications, but glycoprotein IIb/IIIa inhibitors have been shown to increase the clinical and economic costs of bleeding complications. The replacement of heparin with bivalirudin is associated with significant reductions in the costs of antithrombotic therapy and in complications. Reductions in bleeding complications have become a primary target for further improvements in both clinical and economic outcomes.