OBJECTIVES: Biologic treatments had dramatically changed the therapeutics, outcomes and cost of management of psoriasis, a common chronic disease that strongly affects quality of life of patients. The aim of this study was to assess the cost-effectiveness of biologic alternatives currently available in Mexico for treatment of moderate to severe psoriasis from an institutional perspective. METHODS: A decision-tree model was developed to simulate the clinical course of patients treated with etanercept, adalimumab, infliximab or ustekinumab as first-line therapies, as well as treatment associated costs (2-year timeframe with a 5% annual discount rate). Effectiveness measures were the proportion of patients reaching 75% improvement in the Psoriasis Area and Severity Index (PASI-75) and quality adjusted life years gained (QALY´s). Costs considered included: biologics drugs, concomitant medication, medical follow-up and side effects management. Clinical response of alternatives was extracted from published literature, while unit costs were collected from Instituto Mexicano del Seguro Social (IMSS) official databases. Probabilistic sensitivity analyses were completed RESULTS: After two years, the proportions of patients reaching PASI-75 were 59%, 62.1%, 62.7%, and 64.5% for  adalimumab, etanercept, infliximab and ustekinumab, respectively (p=0.077, Friedman test); QALY´s associated to each alternative were: 1.5554, 1.5633, 1.5650 and 1.5695, respectively (p=0.392, Friedman test). Given that in the timeframe considered there are no differences between effectiveness of therapies, a cost-minimization rather than a cost-effectiveness analysis was performed. The expected mean costs per patient were: US$27,281.95, US$25,929.85, US$31,542.76 and US$38,050.59, respectively. Etanercept is US$1,352.1(-5.1%) less costly compared to adalimumab; US$5,612.91(-17.8%) compared to infliximab and US$12,120.74 (-46.74%) compared to ustekinumab (the most costly alternative). CONCLUSIONS: Given that effectiveness of the biologic treatments analyzed is similar over the time-horizon used, etanercept treatment represents the less expensive alternative for the management of moderate and severe psoriasis at IMSS.