OBJECTIVES: . Rheumatoid Arthritis (RA) affects approximately 0.4% of the Latin American population over 16 years old.  Due to its chronic and progressive condition, RA has an important economic and social impact.  The aim is to assess the cost-effectiveness of etanercept in the treatment for moderate to severe RA, with previous antirheumatic drugs (DMARDs) failure, in comparison with the rest of anti-TNF and IL-6 blokers products available in Guatemala, from the healthcare payer’s perspective.  METHODS: . A decision tree model was used to compare the costs and effectiveness of the alternatives, all in combination with methotrexate, in the treatment of RA in adult population of Guatemala.  The alternatives included were: etanercept (comparator), adalimumab, infliximab and tocilizumab.  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 (2011 US$) were obtained from Guatemala´s Ministry of Health databases.  The outcomes were express in costs of success with ACR20 and ACR70 and QALYs gained.  Univariate sensitivity analysis was performed. The time horizon was 2 years.  Discount rate was 5% for costs and health outcomes.  RESULTS: .  Results showed that etanercept gained the highest number of QALYs (1.5423) in comparison with adalimumab (1.5048), infliximab (1.4299) and tocilizumab (1.4955).  Etanercept appeared as the least expensive alternative at both ACR<20 ($69,410.32) and ACR<70 ($176,178.43).  The highest costs were obtained by infliximab, ACR<20 ($139,291.80) and ACR<70 ($612,236.06).  Cost-effectiveness analyses exhibited etanercept as the dominant strategy.  Acceptability curves showed that at the willingness-to-pay of US$8,000/QALY, the probability that etanercept is cost-effective met 100%.  PSA results support the robustness of these findings.  CONCLUSIONS: . Etanercept is the most cost-effective alternative for treating RA against other anti-TNF and IL-6 blockers.  According to <3 GDP per capita ($5,200; 2010) threshold of Guatemala, etanercept is a cost-effective treatment for RA.