Few data exist on the use of aggressive combination therapy with thienopyridines and glycoprotein IIb/IIIa inhibitors in higher risk patients with an acute coronary syndrome(ACS). The aim of this study was to characterize the combined use of these agents and the associated hospital outcomes in patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events. Data from 8,081 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. Of these patients, 5,070(62.7% ) received aspirin and a thienopyridine, and the remainder received aspirin, a thienopyridine, and a glycoprotein IIb/IIIa blocker. The presence of a non-ST-segment elevation myocardial infarction; a history of diabetes or coronary artery bypass surgery; performance of in-hospital catheterization, percutaneous coronary intervention, or coronary artery bypass grafting; and in-hospital use of heparin were independent predictors of the use of triple antiplatelet therapy with aspirin, thienopyridines, and glycoprotein IIb/IIIa blockers. Increased diastolic blood pressure and increased serum creatinine were associated with a failure to prescribe triple therapy. An increased risk of major bleeding during hospitalization was associated with the use of triple antiplatelet therapy(odds ratio 1.6, 95% confidence interval 1.2 to 2.2). Aggressive antiplatelet therapy was used in approximately 2 of every 5 patients presenting with an ACS. Triple therapy was associated with the performance of catheterization and/or percutaneous coronary intervention, as well as high-risk patient features. Although no differences in hospital death rates were evident in patients receiving triple therapy, this population was at significantly increased risk of major bleeding episodes during hospitalization. Few data exist on the use of aggressive combination therapy with thienopyridines and glycoprotein IIb / IIIa inhibitors in higher risk patients with an acute coronary syndrome (ACS). The aim of this study was to characterize the combined use of these agents and the associated hospital outcomes in patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events. Data from 8,081 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. Of these patients, 5,070 (62.7%) received aspirin and a thienopyridine, and the remainder received aspirin, a thienopyridine, and a glycoprotein IIb / IIIa blocker. The presence of a non-ST-segment elevation myocardial infarction; a history of diabetes or coronary artery bypass surgery; performance of in-hospital catheterization, percutaneous coronary intervention, or coronary artery bypass grafting; and in-hospital use of heparin were independent predictors of the use of triple antiplatelet therapy w ith aspirin, thienopyridines, and glycoprotein IIb / IIIa blockers. Increased diastolic blood pressure and increased serum creatinine were associated with a failure to prescribe triple therapy. An increased risk of major bleeding during hospitalization was associated with the use of triple antiplatelet therapy (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). Aggressive antiplatelet therapy was used in approximately 2 of every 5 patients presenting with an ACS. Triple therapy was associated with the performance of catheterization and / or percutaneous coronary intervention, as well as high-risk Although no differences in hospital death rates were evident in patients receiving triple therapy, this population was at significantly increased risk of major bleeding episodes during hospitalization.