OBJECTIVES: Rheumatoid arthritis (RA) affects approximately 60.000 people in El Salvador.  RA has a significant effect on quality of life of patients and it is associated with high costs to society.  The objective is to assess the cost-effectiveness (CE) of etanercept in the treatment for moderate to severe RA, among patients failing previous antirheumatic drugs (DMARDs), in comparison with the rest of anti-TNF and IL-6 blockers products available in El Salvador, from the healthcare payer’s perspective.  METHODS: In order to compare the costs and effectiveness of the alternatives included, a decision-tree was utilized.   The alternatives for treating RA were: etanercept (comparator, 50mg/week), adalimumab (40mg/15 days), infliximab (3-10mg/kg), rituximab (1000mg day 0 and 15, week 16-24) and tocilizumab (8mg/kg/month), all in combination with methotrexate. The effectiveness measures were: American College of Rheumatology (ACR) Response Criteria ACR<20 and ACR<70. Quality utilities were obtained from Health Assessment Questionnaire (HAQ). Local costs (2012 US$) were obtained from official databases from the Social Security of El Salvador.  The outcomes were: total costs of RA and quality-adjusted life years (QALYs) gained. Univariate sensitivity analysis was performed. The time horizon was 1 year.  RESULTS: Etanercept was the least expensive option ($US19,959.82) while infliximab was the most expensive option (US$25,262.66).  The total cost for Adalimumab was $US21,236.14 and $21,301.85 for Rituximab.  Etanercept gained the highest number of QALYs (0.79) compared to adalimumab (0.77), infliximab, (0.73), and rituximab (0.75).  In the CE analyses, etanercept appeared as the dominant strategy. Acceptability curves showed that at the willingness-to-pay level of US$15,300/QALY, etanercept was cost effective with a 100% probability.  Probability sensitivity analysis results support the robustness of these findings.  CONCLUSIONS: Etanercept is the least expensive and most effective option for treating RA in El Salvador.  Etanercept is cost-effective option according to <3 GDP per capita ($7,600; 2011) threshold of El Salvador.