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Introduction: Myelodysplastic syndrome (MDS) comprises a group of clonal hematological disorders, characterized by ineffective hematopoiesis and progressive bone marrow failure. It increases the risk of transformation to acute myeloid leukemia (AML). Therapeutic benefit should include overall survival increase (OS), hematological improvement, transfusion dependence and time to progression to AML decrease. Objective: Assess, from a Mexican health-care perspective, the cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC) plus best supportive care (BSC) for the treatment of adult patients with intermediate-2 and high-risk MDS, who are not eligible for hematopoietic stem-cell transplantation. We developed a cost-effectiveness survival analysis model of three stages: MDS, AML, and death. OS and costs are extrapolated beyond three-year time horizon. Discount rate of 5% was applied. To estimate the model cycle probability transition to mortality state, survival curves were constructed for each treatment arm using individual patient-level data from Study AZA-001. Unitary costs are from public price list, and profiles for the management of MDS and AML were collected separately using a structured questionnaire. Probabilistic sensitivity analyses (PSA) were conducted by simultaneously sampling from estimated probability distributions of model parameters. Results: Overall survival was projected to increase by 72.26 weeks with azacitidine. Incremental expected total costs for azacitidine compared to LDC was MXN$68,045. However, the cost of the drug therapy was lower with azacitidine. The incremental cost-effectiveness ratio (ICER) for azacitidine compared to LDC was MXN$48,932 per life-year gained (LYG). PSA showed that azacitidine was a highly cost-effective option in 96.49% of the simulated cases in MXN$180,000/LYG willingness-to-pay. Conclusions: Compared with LDC, azacitidine represents a cost-effective treatment alternative in patients with MDS from a Mexican perspective.