Case-fatality rates are important for assessing the risks and benefits of anticoagulation in patients with venous thromboembolism (VTE). To summarize case-fatality rates of recurrent VTE and major bleeding events during anticoagulation and recurrent VTE after anticoagulation. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and all evidence-based medicine reviews in the Ovid interface through the second quarter of 2008. 69 articles (13 prospective cohort studies and 56 randomized, controlled trials) that reported on patients with symptomatic VTE who received anticoagulation therapy for at least 3 months and on the rate of fatal recurrent VTE and fatal major bleeding. Two reviewers independently extracted data onto standardized forms. During the initial 3 months of anticoagulation, the rate of recurrent fatal VTE was 0.4% (95% CI, 0.3% to 0.6%), with a case-fatality rate of 11.3% (CI, 8.0% to 15.2%). The rate of fatal major bleeding events was 0.2% (CI, 0.1% to 0.3%), with a case-fatality rate of 11.3% (CI, 7.5% to 15.9%). After anticoagulation, the rate of fatal recurrent VTE was 0.3 per 100 patient-years (CI, 0.1% to 0.4%), with a case-fatality rate of 3.6% (CI, 1.9% to 5.7%). Estimates come from heterogeneous trial and cohort populations and are not derived from patient-level longitudinal data. Differences in case-fatality rates during and after anticoagulation may be attributable to unmeasured patient characteristics. The case-fatality rates of recurrent VTE and major bleeding events are similar during the initial period of VTE treatment. The case-fatality rate of recurrent VTE decreases after completion of the initial period of anticoagulation. When combined with absolute rates of recurrent VTE and major bleeding events, case-fatality rates provide clinicians with a surrogate measure of mortality to balance the risks and benefits of anticoagulant therapy in patients with VTE. Canadian Institute for Health Research and Heart and Stroke Foundation of Ontario.