The QUAZAR AML-001 trial (NCT01757535) showed survival benefits with the maintenance treatment of oral azacitidine(CC-486) for acute myeloid leukemia(AML) in first complete remission. We conducted a cost-effectiveness analysis to explore the costs and benefits of oral azacitidine in AML from the perspective of payers in the United States.We constructed a Markov model to evaluate the economic value of oral azacitidine. The model was conducted with a 10-year time horizon. The health utility scores and until prices of medical costs were acquired from previous studies and GoodRX. The transition probabilities were derived from the survival curves of the QUAZAR AML-001 study. Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER).Compared with placebo, oral azacitidine improved 0.39 QALY, with an increasing cost of $458928.66. The ICER of oral azacitidine is $1176740.15, higher than the willingness to pay (P < 0.05). Deterministic sensitivity analysis showed that the price of oral azacitidine has a significant impact on ICERs (P < 0.05). Probability sensitivity analysis showed that the probability of cost-effectiveness for oral azacitidine is 0.In the United States, oral azacitidine is unlikely to be cost-effective for AML patients at current prices.The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT01757535).