OBJECTIVES: Rheumatoid arthritis (RA) is an inflammatory chronic disease with a prevalence of 0.5 - 1% worldwide. In Latin American countries, prevalence rates vary in the same range. The disease is more frequent in women than in men according international statistics.The goal of this study was to evaluate the yearly cost-effectiveness of biologic therapies in RA patients used in public sector institutions in Ecuador. METHODS: The study was conducted in Guayaquil, Ecuador. A decision tree model was constructed to determine the cost-effectiveness of biologic agents used in rheumatoid arthritis management during 1 year. The model evaluated direct drug costs, complementary tests (blood tests, urine tests, erythrocyte sedimentation rate, and image tests), the number of visits in ambulatory office services, the number and days of hospitalization, and drug administration costs. Biologic treatments analyzed in the study were etanercept (50mg/sc/weekly), adalimumab (40mg/sc/every other week), rituximab (1000mg/ IV- day 1 and day 15) and tocilizumab (8mg/kg/IV every 4 weeks). Efficacy was assessed according to American College of Rheumatology (ACR) criteria and QALYs (Quality Adjusted Life Years) based on published evidence. Costs in the model were based on Ecuadorian Reference costs (2014) and institutional costs. Cost-effectiveness analysis was reported based on Incremental Cost Effectiveness Ratio (ICER). In addition, a stochastic sensitivity analysis was performed. RESULTS: Adalimumab was the most cost-effective biologic therapy per patient in rheumatoid arthritis management with an ICER of -37,586.6 USD per QALYs (dominant therapy); the second cost-effective biologic therapy was rituximab with ICER 12,820.3 USD per QALYs. Etanercept and tocilizumab were less cost-effective therapies. CONCLUSIONS: Adalimumab was clearly the most cost-effective biologic agent in the treatment of rheumatoid arthritis in a large public hospital in Ecuador.