OBJECTIVES:   To review the evidence, submitted to the National Institute of Health and Care Excellence (NICE) by Celgene, on the clinical and cost-effectiveness of azacitidine for the treatment of acute myeloid leukaemia in adults with >30% bone marrow blasts who are not eligible for hematopoietic stem cell transplantation, as part of the NICE Single Technology Appraisal process.  METHODS:  The company’s analysis was based on data from a randomized controlled trial, AZA-AML-001. The trial was conducted to determine the efficacy and safety of azacitidine against a conventional care regimen (CCR) comprised of three individual comparators: intensive chemotherapy followed by best supportive care (BSC) upon disease relapse or progression, non-intensive chemotherapy followed by BSC, and BSC alone. The primary trial end point, overall survival, was affected by treatment switching in both arms. The company’s economic evaluation was based on a partitioned survival model with four states: Remission, Non-remission, Relapse/Progressive disease and Death. We critically appraised the company’s submission; assessed the replicability and internal validity of their analysis using individual-patient data from AZA-AML-001; and examined the effect on incremental cost-effectiveness ratio (ICER) of crossover, and of altering model assumptions to reflect current UK practice. RESULTS:  In the company’s analysis, the base-case ICER of azacitidine vs. CCR was £20,648 per quality-adjusted life-year (QALY) gained; in their probabilistic sensitivity analysis, the ICER was £17,423. After our amendments to Celgene’s model, the respective ICERs were £273,308 and £277,123 per QALY. In all our exploratory analyses, the ICER exceeded NICE’s threshold range of £20,000 to £30,000 per QALY gained. The major drivers of the increase in the ICER were model corrections related to healthcare resource use, and calibration of the number of treatment cycles (for consistency with AZA-AML-001).  CONCLUSIONS:   After considering these analyses and statements from patient and clinical experts, the NICE Appraisal Committee did not recommend azacitidine for this indication.