This meta-analysis and systematic review included 9 studies comparing novel oral anticoagulants (with or without initial treatment with heparin) to vitamin K antagonists (always with inital treatment with heparin) in patients with acute venous thromboembolism. From the 9 studies, 16 701 patients were assessed with regards to the efficacy of the drugs and 16 611 were evaluated on safety. Results indicated that there was no difference between any of the anticoagulants compared to the conventional treatment with regards to the rate of recurrent events and mortality. Rivaroxaban was the only novel anticoagulant that resulted in a significant reduction in major bleeding compared to conventional treatment.