Platelet glycoprotein (GP) IIb/IIIa receptor antagonists are being used with increasing frequency in the settings of percutaneous coronary interventions and acute ischemic syndromes. The development of bleeding complications following GPIIb/IIIa blockade represents a significant limitation to its effectiveness. Baseline characteristics predictive of future bleeding events in patients receiving platelet GPIIb/IIIa receptor antagonist include older age, low body weight, evolving myocardial infarction, and female sex. In patients undergoing percutaneous coronary interventions with adjunctive GPIIb/IIIa inhibition, the risk of bleeding, particularly from the femoral vascular access site, may be reduced through the use of low-dose, weight-adjusted heparin (70 U/kg), avoidance of postprocedural heparin, and early vascular sheath removal. Strategies to reduce the incidence of bleeding complications in patients receiving GPIIb/IIIa inhibitors are proposed in this article.