INTRODUCTION: The ALCYONE trial found that daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) can significantly improve progression-free survival (PFS) and overall survival (OS) for patients with transplant-ineligible, newly diagnosed multiple myeloma (MM) in China. In the present study, we evaluated the cost-effectiveness of D-VMP versus VMP for patients with newly diagnosed MM in China. METHODS: A Markov model was used to estimate the cost-effectiveness of frontline D-VMP versus VMP for MM. The life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. A series of sensitivity analyses was performed to assess the robustness of the model and address uncertainties in variable estimates. Subgroup analysis was also performed. RESULTS: D-VMP provided an additional 2.99 LYs and 1.67 QALYs compared with VMP, with incremental $64,920 per LY and $116,015 per QALY gained. The results of the univariable sensitivity analysis showed that the parameter that had the greatest impact on the ICER was the cost of subsequent treatment and daratumumab. When the cost of daratumumab was 100%, 70%, 50%, and 30% of the current price, the probability of D-VMP being cost-effective was 2.49%, 16.11%, 39.09%, and 70.73% at the willingness-to-pay (WTP) threshold of $30,950/QALY, respectively. The results demonstrated that the ICER in all subgroups remained > $30,950/QALY. CONCLUSION: D-VMP versus VMP is likely to exceed the commonly accepted values of cost-effectiveness in patients with transplant-ineligible, newly diagnosed MM in China.