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Introduction and Objectives: To investigate how thienopyridine treatment, with or without associated fibrinolysis, affects the rates of major bleeding and inhospital death in patients with ST-elevation myocardial infarction (STEMI)., Methods: The rates of major bleeding and in-hospital death were studied in 14,259 consecutive patients with STEMI. During hospitalization, 5340 (38%) received thienopyridines, 3007 (21%) received fibrinolytic drugs, and 2044 (14%) received both., Results: Major bleeding occurred more frequently in patients who received thienopyridines with or without fibrinolytics, in 4.6% and 4.1%, respectively, compared with 2.3% in those who received fibrinolytics alone and 2.8% in those who received neither (P< .001). Multivariate analysis, which included adjustments for risk factors for bleeding, percutaneous coronary intervention and cardiac catheterization, showed that thienopyridine treatment was an independent risk factor for bleeding (odds ratio=1.68; 95% confidence interval, 1.23-2.31). In-hospital mortality was lower in patients who received a thienopyridine, and such treatment was an independent predictor of lower mortality (odds ratio=0.50; 95% confidence interval, 0.39-0.60)., Conclusions: Thienopyridine treatment was associated with an increased risk of major bleeding but also with a better in-hospital prognosis. These findings in unselected patients with STEMI, who are representative of those seen in daily clinical practice, complement, but do not replace, the data obtained in randomized clinical trails of selected patients.