OBJECTIVES: To present the first cost-effectiveness analysis comparing standard prophylaxis, i.e. prophylaxis with recombinant factor VIII from 2 to 16 years old then switching to on-demand treatment, with on-demand treatment, in treating severe hemophilia A patients in China. METHODS:  The cost-effectiveness analysis was conducted from a societal perspective with a lifetime horizon. A Markov model was developed to reflect clinical practice in China’s setting. Major events, including joint and total bleeds, major surgery, intracerebral hemorrhage, inhibitor development, outpatient visits, productivity loss and death were all considered. Clinical data and utility values were derived from multiple published studies, and resource utilization and costs were estimated based on studies conducted in China and opinions from local experts. Analysis results were presented with incremental cost-effectiveness ratio (ICER). A threshold of 3 times local GDP per capita was applied. To test the robustness of base-case results, one-way and probabilistic sensitivity analyses were performed. Besides, scenario analyses were also undertaken to assess the impact of low-dose prophylaxis and no treatment for inhibitor. RESULTS:  The base-case analysis favored standard prophylaxis as it is associated with lower costs (1,278,101 CNY) and higher QALYs (6.24 QALYs) per patient in lifetime. According to the one-way sensitivity analysis, this result was sensitive to the dosage of infusion in both strategies, the frequency of infusion in standard prophylaxis, and the frequency of bleeding. Probabilistic sensitivity analysis results demonstrated that over 80% simulations were lower than the cost-effectiveness threshold. Low-dose prophylaxis was also considered dominant compared with on-demand treatment. Without consideration of treatment for inhibitor, the ICER was estimated at 87,794 CNY per QALY gained, implying a cost-effective option for patients with severe hemophilia A in China. CONCLUSIONS:  In the local context of China, standard prophylaxis for hemophilia A patients is a dominant strategy compared with standard on-demand treatment.