OBJECTIVES: To estimate the cost-effectiveness of Beclomethasone/Formoterol (BF) versus Fluticasone/Salmeterol (FS) in the treatment of adult out-patients with moderate to severe asthma from the perspective of the Society in Spain.  METHODS: A Markov model was developed with five asthma health states: successful control, sub-optimal control, outpatient-managed exacerbation, inpatient-managed exacerbation, and death. Weekly transition probabilities were derived from the published 12-weeks ICAT SE study. Resources utilization were obtained from a published Spanish study designed ad-hoc to ascertain healthcare resources utilization, the so-called lost-workday-equivalents, and corresponding costs related with treatment of asthma in the year 2011. Time horizon was set at 12 weeks in the basecase scenario. Effectiveness was expressed as quality-adjusted life years (QALY) gain. The cost-effectiveness was expressed as an incremental cost effectiveness ratio (ICER). Bootstrapping techniques (10,000 re-samples) were used to obtain the probabilistic ICER, its 95% percentile confidence interval (CI) and the cost-effectiveness acceptability curve. Univariate and probabilistic sensitivity analysis (PSA) were also applied and included, among others, extension of the horizon to one year and the perspective of the NHS only.  RESULTS: Compared with FS, BF was associated with a slightly increase in QALY gain; 0,7974 vs. 0,7945 while differential costs were always lower favoring BF and yielding to a mean ICER dominant (95% CI: dominant; €46,930) per QALY gained. In 96% of re-samples, the ICER was below the threshold of €30,000 per QALY, considered as cost-effective in Spain. Univariate and PSA were robust and confirmed results of the basecase scenario. CONCLUSIONS: From the Spanish societal and NHS perspectives in year 2011, Becomethasone/Formoterol produced similar QALY gain at a lower cost when compared with Fluticasone/Salmeterol in a highly meaningful number of replications and scenarios. Thus, Beclomethasone/Formoterol may be considered a cost-effective alternative in the treatment of moderate to severe asthma in Spain.