OBJECTIVES:  The aim of this study was to evaluate the cost-effectiveness of apixaban and enoxaparin for the universal prophylaxis of venous thromboembolism (VTE) and associated long-term complications in Chinese patients after Total knee replacement (TKR). METHODS:  A decision model, which included both the acute VTE (represented as a decision tree) and the long-term complications (represented as a Markov model), was developed to assess economic outcomes of the two strategies for Chinese patients after TKR. Transition probabilities in acute VTE were derived from one randomized controlled study ADVANCE2 of patients after TKR. Transition probabilities in the long-term complications after acute VTE, utilities and costs were derived from published literature and local health care data sources. One-way and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty concerning the model parameters. Quality-adjusted life year (QALY) and direct medical costs were reported over a five-year horizon. Incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS:  Thromboprophylaxis with apixaban was estimated to be associated with higher cost (US $68.36) and more health benefits (0.0006 QALY) in comparison with enoxaparin, resulting in an ICER of US $108,497 per QALY gained, which was above 3×GDP per capital 2014 in China (US $22,140). One-way sensitivity analyses found the cost of apixaban and the probability of pulmonary embolism for apixaban and enoxaparin had the considerable impact on the model outcomes. CONCLUSIONS:  Apixaban was found to be not cost-effective compared with enoxaparin. It means that compared with enoxaparin, use of apixaban for VTE prophylaxis after TKR did not represent good value for money at the acceptable threshold in China.