This meta-analysis and systematic review included 37 studies comparing low molecular-weight heparins (LMWHs) to other anticoagulants in patients undergoing major orthopedic surgery. The results indicated that LMWHs were more effective and also led to fewer cases of bleeding than unfractionated heparins. LMWHs led to fewer cases of deep vein thrombosis events than vitamin K antagonists, but resulted in greater bleeding. In contrast, factor Xa inhibitors increased bleeding but were more effective than LMWHs. Lastly, direct thrombin inhibitors were more effective than LMWHs in reducing venous thromboembolism and proximal deep vein thrombosis events.