OBJECTIVES: Rheumatoid Arthrtis (RA) leads to significant impact on management costs and patient’s quality of life. In Venezuela, annual per capita cost for RA management increased from 698USD in 1997 to 3494USD in 2002. Biologic treatment after disease-modifying antirheumatic drugs fail is an alternative, but their high cost represents a challenge for decision makers. This study aims to perform cost-effectiveness and cost-utility analysis of biologic alternatives for moderate to severe RA in Venezuela. METHODS: An economic analysis was developed through a decision-tree model to simulate RA evolution after treatment with etanercept (basecase treatment), adalimumab, infliximab, tocilizumab or rituximab as first-line therapies and their associated costs over a 12-month time horizon. Therapy continuation or switch was evaluated at week 24. Effectiveness measures were ACR70 response and quality adjusted life years (QALYs) gained. Direct medical costs included biologics, concomitant drugs, medical follow-up and adverse events management. Clinical response was extracted from published literature, while costs were collected from Venezuelan public official databases. Probabilistic sensitivity analyses were performed through Monte Carlo Simulation second-order approach. RESULTS: In base case analysis estimated effectiveness resulted in [ACR70,QALY]: etanercept [31.3%,0.79]; adalimumab [18.1%,0.77]; infliximab [12.8%,0.73]; tocilizumab [21.1%,0.77] and rituximab [11.9%, 0.75]. Expected mean costs per patient were 13,588USD, 15,451USD; 15,950USD; 18,705USD and 14,350USD, respectively. In cost-effectiveness and cost-utility analysis, etanercept was the least costly and the most effective alternative being cost-saving in all comparisons: 5117USD less than tocilizumab (most costly alternative); 19.4% more patients met ACR70 response regarding rituximab (the least effective alternatives); incremental utility reached +0.0576 QALYs versus infliximab. Acceptability curves showed that etanercept regardless willingness to pay would be the most cost-effective biologic. CONCLUSIONS: Due to its lower costs and favorable effectiveness profile, etanercept is dominant regarding ACR70 response and QALYs gained over other biologic treatments in the management of RA at Venezuelan public health care system.