OBJECTIVES The present study aims to estimate the cost-effectiveness of etanercept compared to golimumab in the treatment of patients with Rheumatoid Arthritis (RA) in Portugal.   METHODS A model was adapted to assess the cost-effectiveness of etanercept in the treatment of RA. We performed a comparison of the combination of etanercept + methotrexate and golimumab + methotrexate. Dosage of etanercept was 50mg on a weekly basis, whereas for golimumab it was 50 mg once a month. The model is an individual simulation model and takes a lifetime perspective. Outcomes are expressed in QALYs, using the HAQ score to measure quality of life. The clinical parameters used in the model take into account the results from a MTC of clinical trials. In order to adapt the model to the Portuguese context, several adjustments were made to its original version. These mainly relate to mortality rates by gender and to the unit costs of medical resources, such as drugs, medical visits, admissions, ancillary tests and so on, that were obtained from public official sources. We applied a 5% discount rate and conducted an analysis for a hypothetical cohort of 1,000 patients.  RESULTS The treatment of RA with etanercept is more expensive than that with the comparator. Nevertheless, QALYs gained do compensate for the additional costs. Overall, ICER is €12,853, which is below the usual willingness to pay threshold used in Portugal. A sensitivity analysis was carried out, which confirmed the robustness of these results.  CONCLUSIONS According to our analysis, etanercept is a cost-effective alternative versus golimumab for the treatment of rheumatoid arthritis. Its main advantage over the selected comparator relates to the associated improvements in health related quality of life.