OBJECTIVE To evaluate the economic value of denosumab compared with alendronate and zoledronate in the treatment of postmenopausal women and men with osteoporosis (OP) from the perspective of Chinese health system. METHODS Markov model was built and the treatment period was set to 5 years. The clinical efficacy, health utilities and cost data were obtained from published literature. Lifetime health outcomes and costs were calculated for each intervention with the consideration of adherence and treatment residual effect. With the incremental cost-effectiveness ratio as the index, the threshold of a willingness-to-pay was set as 3 times GDP per capita. Scenario analysis and sensitivity analysis were conducted to test the result's robustness. RESULTS Denosumab was dominant compared with alendronate or zoledronate in postmenopausal women with OP, associated with higher QALY by 0.06 and 0.03 and lower costs by CNY1 471 and CNY3 327 respectively. Denosumab was also dominant compared with alendronate or zoledronate in men with OP, associated with higher QALY by 0.07 and 0.03 and lower CNY2 costs by 158 and CNY3 526 respectively. Sensitivity analyses verified the robustness of study results. CONCLUSION In the treatment of postmenopausal women and men with OP, denosumab has absolute advantages over alendronate and zoledronate, and should be a preferred or long-term treatment in clinical practice.