The angiographic severity of coronary stenoses may not predict sites of subsequent acute coronary events, inasmuch as rupture of atheromatous plaque with thrombosis in relatively mildly stenosed vessels may underlie many acute coronary syndromes. The intact endothelium normally prevents platelet activation, but the intimal injury associated with endothelial denudation and plaque rupture exposes subendothelial collagen and von Willebrand factor, which support prompt platelet adhesion and activation. Circulating platelets can adhere either directly to collagen or indirectly, via the binding of von Willebrand factor, to the glycoprotein Ib/IX complex. Local platelet activation promotes thrombus formation and additional platelet recruitment by supporting cell surface thrombin formation and releasing potent platelet agonists, such as adenosine 5-diphosphate, serotonin, and thromboxane A2. The central role of platelet activation in acute coronary syndromes is supported by increased plateletderived thromboxane and prostaglandin metabolites detected in patients with acute coronary syndromes1 and the clear clinical benefit of treatment with aspirin for prevention of acute coronary events. 2