Warfarin is the only domestic vitamin K antagonist (there are other similar drugs in Europe), and it has been the standard of care for acute venous thromboembolism (including lower extremity deep vein thrombosis and pulmonary embolism) for decades. However, a number of new oral anticoagulants (or oral direct anticoagulants) have emerged in recent years, including rivaroxaban, dabigatran, apixaban, and edoxaban, which have become challengers to the standard regimen of the past. To compare the effectiveness and side effects of the newer drugs with warfarin, researchers in the Netherlands did a systematic review and meta-analysis of studies comparing the two classes of anticoagulants. They analyzed two clinical trials of rivaroxaban and one each of dabigatran, apixaban, and edoxaban, for a total of 24,455 patients with acute venous thromboembolism. The recurrence rates of venous thromboembolism were similar between the two treatment regimens (2.0% and 2.2% for the newer drugs and warfarin, respectively), with no significant difference in relative risk (0.88). Fatal pulmonary embolism occurred in 9 patients each (0.07%), and the relative risk for all-cause mortality was 0.97. The incidence of major bleeding was lower with the newer drugs than with warfarin (1.1% and 1.7%, respectively; relative risk 0.6), with similar results for nonfatal intracranial hemorrhage (0.09% and 0.25%, respectively; relative risk 0.39) and fatal bleeding (0.06% and 0.17%, respectively). 0.06% and 0.17%, respectively; relative risk 0.36). Gastrointestinal bleeding was more frequent with dabigatran (0.71% vs. 0.39%). There was no significant difference in prognosis between dabigatran, apixaban and edoxaban compared with rivaroxaban. The advantages of the newer oral anticoagulants compared to vitamin K antagonists are more predictable anticoagulation strength, fewer drug interactions, and no need for monitoring. Disadvantages are the absence of reversal drugs and the high price. Now, we should add to the advantages: better safety and comparable efficacy.