Objective To systematically assess the therapeutic effect of rivaroxaban and enoxaparin on preventing deep venous thrombosis after major orthopedic operation. Methods Such databases as MEDLINE, EMbase, The Cochrane Library (Issue 3, 2009), Current Controlled Trials, The National Research Register, CBM, and CNKI were searched from their establishment to December 2009 in whatever language. Related journals were handsearched as well. Randomized controlled trials (RCTs) of comparing therapeutic effects of rivaroxaban and enoxaparin on preventing deep venous thrombosis after major orthopedic operation were included. Data were extracted and their quality was evaluated, and meta-analyses were conducted by using RevMan 5.0.25 software. Results Seven RCTs with 15 458 patients were included. The results of meta-analyses showed that compared with enoxaparin, rivaroxaban reduced the end risk of the primary efficacy to 60% (RR=0.40, 95%CI 0.28 to 0.57, Plt;0.000 01) and reduced the end risk of the main secondary efficacy to 71% (RR=0.29, 95%CI 0.15 to 0.56, Plt;0.000 01), and the end risk of other efficacy to 56% (RR=0.44, 95%CI 0.29 to 0.66, Plt;0.000 01). During the treatment, rivaroxaban and enoxaparin displayed similarity in terms of the incidence of serious bleeding events (RR=1.16, 95%CI 0.68 to 1.999, P=0.59) and the secondary safety endpoint. Conclusion Rivaroxaban is effective in preventing deep venous thrombosis after major orthopedic operation and can significantly reduce the risk of postoperative deep vein thrombosis.