OBJECTIVES: To estimate the cost/efficacy ratios of biologics authorized in Spain in 2009 (adalimumab, etanercept, infliximab and ustekinumab) in the management of moderate-severe psoriasis. METHODS: A model for economic evaluation (decision tree) was built for the treatments according to the available scientific evidence. The payer perspective (National Health System) was used, only considering drug cost and assuming zero cost for placebo. In the case of weight-dependent dosing, the weight of the study participants was adjusted by age and sex to the standard Spanish population corrected by the weight increment in individuals with psoriasis. The Psoriasis Area Severity Index (PASI) 75 criterion (improvement of 75% from baseline PASI) was used as indicator of efficacy. The incremental efficacy (calculated as the proportion of patients responding with PASI 75 criterion in the biologic group minus the proportion who respond in the placebo group) was assigned according to the outcomes of clinical trials at the period of time defined in the primary efficacy outcome. When more than one trial was available per treatment, a meta-analysis was undertaken (DerSimonian-Laird method). Uncertainty was tested by deterministic sensitivity analysis, building scenarios with the confidence intervals at 95% for costs and efficacy. RESULTS: The incremental efficacy in the baseline scenario ranged from 31.19 % (etanercept: 25 mg twice a week at 12 weeks of treatment) to 78.35% (infliximab: 5 mg/Kg at 24 weeks of treatment). The efficiency in terms of cost/efficay, in the baseline scenario, ranged from €8,013 (adalimumab at 16 weeks) and €17,981 (ustekinumab: 90 mg at 12 weeks) per PASI 75 responder. In the sensitivity analysis, adalimumab remains as the most efficient biologic on the most and least favourable scenarios. CONCLUSIONS: Of the biologic agents authorized in Spain for treating moderate-severe psoriasis, the most efficient in terms of cost/efficacy is adalimumab.