OBJECTIVES: Biologic treatment after systemic drugs fail in psoriasis is indicated for obtaining clinical response, what could avoid associated comorbidities. Regarding biological drugs approved for psoriasis, etanercept effectiveness is not lost in retreatment regimens, which allows continuous or paused therapeutic schemes. This study aims to perform cost-effectiveness and cost-utility analyses of biologic alternatives for moderate to severe psoriasis in Venezuela, from a public payer´s perspective. METHODS: A decision-tree model simulates psoriasis evolution after treatment with etanercept continuous (50mg twice a week for 12 weeks, followed by 25mg twice a week) or paused (12-week treatment cycle and 12-week interruption), adalimumab (80mg at first week, followed by 40mg in the second week, then 40mg every 2 weeks), infliximab (5 mg/kg at weeks 0, 2 and 6, then every 8 weeks) or ustekinumab (45mg in weeks 0 and 4, then 45mg every 12 weeks) and their associated costs in a 96-week time horizon. Therapy continuation or switch was evaluated at week 24. Effectiveness measures were PASI 75 success rate and quality adjusted life years (QALY) gained. Costs included biologicals, medical follow-up and adverse events management, from Venezuela official databases (values represented 2010 USD). Probabilistic sensitivity analyses were performed through Monte Carlo simulation. A 5% discount rate was applied for costs and benefits. RESULTS: Effectiveness resulted in [PASI 75, QALY]: etanercept [51.3%, 1.5360], adalimumab [50.5%, 1.5339], infliximab [37.2%,1.5001] and ustekinumab [43.6%, 1.5164]. Treatment costs [continuous, paused] were [16,741USD, 15,692USD], [17,846USD, 19,742USD], [35,685USD, 33,980USD] and [27,569USD, 26,922USD], respectively. Etanercept represented the least costly in all comparisons. Acceptability curves showed etanercept in continuous and paused schemes as the most cost-effective biologic. CONCLUSIONS: In this analysis, due to its lower costs and favorable effectiveness profile, etanercept showed to be cost-saving in both continuous and paused treatment schemes regarding PASI 75 success rate and QALY’s gained.