Abstract: OBJECTIVE To evaluate the efficacy and safety of edoxaban and low molecular heparin in the prevention of venous thromboembolism (VTE) after major orthopedic surgery. METHODS The Cochrane Library, PubMed, EMBASE, CNKI, WanFang, VIP database (VIP) were searched. All the randomized controlled trials of edoxaban compared with low molecular heparin to prevent VTE after orthopedic surgery were collected. All data were analyzed by RevMan 5.3.5. RESULTS Five RCTs involving 2 585 patients were included. Compared with low molecular heparin, edoxaban reduced the total VTE eventsRR=0.47, 95%CI (0.38, 0.56), P<0.000 01 and reduced the asymptomatic deep vein thrombosis eventsRR=0.47, 95%CI (0.31, 0.71), P=0.000 4. The total bleeding events of edoxaban was higher than the low molecular heparinRR=1.22, 95% CI (1.01, 1.49), P=0.04. In the subgroup analysis different doses of edoxaban reduced the total VTE events and the incidences of total bleeding in edoxaban 15 mg and 30 mg were no significant difference compared with low molecular heparin. CONCLUSION Edoxaban is superior to low molecular heparin in the prevention of VTE after major orthopedic surgery, but the total bleeding was higher. The 15 mg and 30 mg edoxban may be safe doses.