OBJECTIVES: In patients with chronic myeloid leukaemia (CML), first line treatment with imatinib therapy is beneficial. In cases of imatinib failure, second-generation tyrosine kinase inhibitors (TKIs) are recommended. Omacetaxine has a novel mode of action and acts independently of TKIs, thus it may have therapeutic advantages for patients who have developed resistance to TKI therapy and have no available treatment options. The objective was to develop a health economic model to estimate the cost-effectiveness of omacetaxine in the treatment of CML. METHODS: A cost-utility Markov model was developed to capture the progression of CML and treatment effects. The model was developed from the perspective of the French healthcare system. Patients entered the model treated either with omacetaxine or standard care, in one of three phases: chronic, accelerated or blast phase, having failed on imatinib therapy (through resistance or intolerance). Patients then moved to states of response, no response, or death. Survival estimates for non-responding and responding patients were taken from studies 202 and 203. These were extrapolated using parametric curve fits to estimate survival beyond the end of the trial. Resource use was based on the trial and from the expert opinion of a panel of French clinicians. Unit costs and utilities were elicited from the literature. One-way and probabilistic sensitivity analyses (PSA) were performed. RESULTS: The deterministic results demonstrated that treatment with omacetaxine is cost-effective at a threshold of €30,000. Sensitivity analysis showed that results were most sensitive to cost of omacetaxine, utility score and survival benefit. PSA results showed that the model was sufficiently robust to parameter uncertainty. CONCLUSIONS: The analysis demonstrated that omacetaxine is cost-effective in the treatment of CML patients who are resistant to TKI therapy and have no available treatment options.