BACKGROUND: Venous thrombosis represents a significant complication after deceased-donor liver transplantation, yet there are currently no established protocols for thromboprophylaxis after deceased-donor liver transplantation. The aim of this study was to evaluate the efficacy and safety of prophylactic anticoagulation in patients undergoing deceased-donor liver transplantation. METHODS: A dual-centre RCT of patients assigned to receive either enoxaparin or normal saline after liver transplantation was conducted. The primary efficacy outcome was the incidence of venous thrombosis (portal vein thrombosis and deep vein thrombosis) and the primary safety outcome was the incidence of major bleeding. RESULTS: A total of 462 patients were recruited. In the intention-to-treat analysis, 89 patients (19.3%) experienced venous thrombosis and 141 patients (30.5%) experienced major bleeding within 90 days after transplantation. No significant differences were observed in the incidence of venous thrombosis, portal vein thrombosis, or deep vein thrombosis between the two groups in the intention-to-treat cohort. The anticoagulant group demonstrated a markedly elevated incidence of major bleeding (35.5% versus 25.5%, P = 0.020). Subgroup analysis revealed that anticoagulation was associated with a lower risk of deep vein thrombosis in hepatocellular carcinoma patients (HR 0.44 (95% c.i. 0.23 to 0.86), P = 0.016), without a significantly higher risk of major bleeding. CONCLUSION: Use of prophylactic anticoagulation with enoxaparin is associated with a significantly higher incidence of major bleeding in patients undergoing deceased-donor liver transplantation, rather than a lower likelihood of venous thrombosis. REGISTRATION NUMBER: ChiCTR2000032441 (www.chictr.org.cn).