We reviewed our database of 312 patients with pulmonary embolism who received thrombolysis in five clinical trials. At baseline, none had a history of stroke, internal bleeding within 6 months, surgery within 10 days, or occult blood in stool. Sixty-six major bleeding episodes occurred within 72 hours of administering thrombolysis in 61 (20%) patients: bleeding at the catheterization site (34 cases), gross hematuria (9), intracranial hemorrhage (5), and 18 other bleeding episodes that led to at least a 10% hematocrit decrease. Patients with a major bleeding complication were on average older than patients with no hemorrhagic complication (mean age 62.9 +/- 1.9 years vs 56.2 +/- 1.1 years; p = 0.005). In an adjusted analysis, there was a fourfold increased risk of bleeding among patients older than 70 years compared with patients younger than 50 years (relative risk [RR] 3.9; 95% confidence interval [CI] 1.7 to 8.9). By using age as a continuous variable, we found a 4% (RR 1.04; 95% CI 1.02 to 1.06) increase in risk of bleeding for each incremental year of age. In addition, patients with higher body mass index had an increased risk of bleeding. Patients who had undergone catheterization had a five times greater risk of bleeding (RR 5.2; 95% CI 1.5 to 17.8). In summary, increasing age, larger body mass index, and catheterization predisposed to bleeding complications after pulmonary embolism thrombolysis.