OBJECTIVES: To estimates cost and effectiveness of beclomethasone/formoterol extrafine, fluticasone/salmeterol and budesodine/formoterol in the treatment of moderate to severe persistent asthma in Spain. METHODS: A Markov model was developed to represent the transition of a cohort of patients with moderate to severe persistent asthma through different health states: patients free of symptoms, patients with exacerbations and patients without exacerbations. Efficacy data was obtained from observational studies. Deterministic results were estimated and a probabilistic sensitivity analysis was conducted using statistical distributions in order to capture parameter uncertainty in the decision model. Treatment costs were obtained from literature review and a panel of clinical experts. Costs were referred to year 2009 and a time horizon of 12 weeks was chosen. Results were presented as expected cost per QALY and represented in cost-effectiveness acceptability curves (CEACs). RESULTS: In the deterministic analysis, the expected cost per patient was greater in the fluticasone/salmeterol cohort (€333) and the budesodine/formoterol cohort (€300) in comparison with the beclomethasone/formoterol cohort (€292). The estimated effectiveness was the same in the three cohorts. In the probabilistic analysis CEACs showed that the probability that the treatment with beclomethasone/formoterol was more cost-effective than the treatment with fluticasone/salmeterol and budesodine/formoterol using alternative values for the maximum value that the health service would be willing to pay for an additional QALY gained was greater in the beclomethasone/formoterol cohort. CONCLUSIONS: When beclomethasone/formoterol extrafine has been compared to fluticasone/salmeterol and budesodine/formoterol we may conclude that the first one is a dominant strategy. Results from probabilistic sensibility analysis show that the choice of optimal strategy is independent on the maximum that the health service is prepared to pay per additional QALY gained because beclomethasone/formoterol extrafine has a greater probability of being cost-effective for all threshold values.