OBJECTIVES:  To asses the cost-effectiveness relationship of dasatinib in comparison to high dose of imatinib in the treatment of CML in patients with imatinib-resistant chronic myeloid leukemia in Spain. METHODS: A Markov model was developed to estimate, in the long term, the costs and clinical outcomes (life years gained and quality adjusted life years gained) of dasatinib compared to imatinib in imatinib-resistant patients. Four health states were considered in the analysis: Chronic phase; Accelerated phase; Blast phase; and Death. Cycle length is on a monthly basis and health effects and costs were counted until all patients reached the “death” health state. The efficacy outcomes are estimated from a direct comparison derived from the clinical trial BMS 017. The health care resource use has been set up by a Spanish clinical expert and direct costs are in euros (2009). The perspective used is the Spanish Health System. Both costs and effects were discounted annually at 3.5%. The robustness of the results was tested in deterministic sensitivity analyses. RESULTS: In the base case scenario, treatment with dasatinib proves to be a dominant option with a lower total cost and a higher level of effectiveness (potential cost saving of €56,995 and 0.19 QALY gained). The sensitivity analysis indicates that dasatinib remains as a dominant alternative in front of changes in the most relevant variables: costs; utility values; age at the start of the treatment; time horizon; and discount rate. CONCLUSIONS: Compared to imatinib, dasatinib shows a slower disease progression with relatively lower direct medical costs. Dasatinib can be regarded as a dominant treatment option in patients with imatinib-resistant CML in the Spanish Health System.