One hundred four patients at Brigham and Women's Hospital who received alteplase for acute pulmonary embolism were evaluated. Major bleeding occurred in 20 patients (19.2%). The principal site of bleeding was unknown in 9 (45.0%), gastrointestinal in 6 (30.0%), retroperitoneal in 3 (15.0%), intracranial in 1 (5.0%), and splenic in 1 (5.0%). Independent predictors of major hemorrhage were the administration of catecholamines for systemic arterial hypotension (odds ratio [OR] 115, 95% confidence interval [CI] 9.4 to 1,410.9, p < 0.001), cancer (OR 16.0, 95% CI 3.2 to 80, p = 0.004), diabetes mellitus (OR 9.6, 95% CI 1.7 to 54, p = 0.010), and elevated international normalized ratio before fibrinolysis (OR 5.8, 95% CI 1.5 to 22, p = 0.012).