CONTEXT: Benefits of recombinant activated factor VII (rFVIIa) in hemorrhage may be lost because of thromboembolic events (TAE). METHOD: MEDLINE, EMBASE, BIOSIS, CINAHL, Science Citation Index Expanded, clinicaltrials.gov were searched for placebo controlled trials of rFVIIa in patients without hemophilia. Reports of 22 randomized controlled trials were selected for analysis. Results were pooled using random effects models to calculate the odds ratios (OR) with 95% confidence interval (CI). Subgroup analyses were predetermined. RESULTS: Among 3184 participants, 478 (15.0%) died and 249 (7.8%) had TAE. Additional blood transfusion was required in 517 (41.2%) of 1256 subjects. Patients receiving rFVIIa were less likely to need additional blood transfusions (OR, 0.54; 95% CI, 0.34-0.86) than patients receiving placebo. Mortality was not increased but may be reduced (OR, 0.88; 95% CI, 0.71-1.09). Reduction in mortality was more likely if rFVIIa was given therapeutically (OR, 0.87; 95% CI, 0.70-1.09) rather than prophylactically (OR, 1.00; 95% CI, 0.37-2.68). Differences in the pooled analysis of TAE were not statistically significant (OR, 1.17; 95% CI, 0.87-1.58) but the incidence of arterial TAE was likely higher in patients receiving rFVIIa (OR, 1.50; 95% CI, 0.93-2.41) although no differences were seen with respect to venous TAE (OR, 0.76; 95% CI, 0.49-1.15). CONCLUSIONS: Use of rFVIIa reduces the need for blood transfusion and it may reduce mortality, especially if the dose of rFVIIa is limited to therapeutic doses of 90 mug/kg. It does not increase the risk of venous thrombosis but it may increase the risk of arterial thrombosis.