In patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and fatal bleeding during anticoagulation may help to guide intensity and duration of therapy. We aimed to provide estimates of the case-fatality rate (CFR) of recurrent VTE and major bleeding during anticoagulation in a 'real life' population, and to assess these outcomes according to the initial presentation of VTE and its etiology. The study included 41,826 patients with confirmed VTE from the RIETE registry who received different durations of anticoagulation (mean 7.8 +/- 0.6 months). During 27,110 patient-years, the CFR was 12.1% (95% Cl, 10.2-14.2) for recurrent VTE, and 19.7% (95% Cl, 17.4-22.1) for major bleeding. During the first three months of anticoagulant therapy, the CFR of recurrent VTE was 16.1% (95% Cl, 13.6-18.9), compared to 2.0% (95% Cl, 0-4.2) beyond this period. The CFR of bleeding was 20.2% (95% Cl, 17.5-23.1) during the first three months, compared to 18.2% (95% Cl, 14.0-23.2) beyond this period. The CFR of recurrent VTE was higher in patients initially presenting with PE (18.5%; 95% Cl, 15.3-22.1) than in those with DVT (6.3%; 95% Cl, 4.5-8.6), and in patients with provoked VTE (16.3%; 95% Cl, 13.6-19.4) than in those with unprovoked VTE (5.5%; 95% Cl, 3.5-8.0). In conclusion, the CFR of recurrent VTE decreased over time during anticoagulation, while the CFR of major bleeding remained stable. The CFR of recurrent VTE was higher in patients initially presenting with PE and in those with provoked VTE.