OBJECTIVES To determine the incremental cost-effectiveness ratio (ICER) of etanercept (a fusion protein) versus other two anti-TNF-á monoclonal antibodies used in the treatment of RA, based on a payer perspective. METHODS A decision analytic model was developed to compare the cost-effectiveness of etanercept (25mg twice-weekly) versus adalimumab (40mg every other week) and infliximab (3mg/Kg in the weeks 0, 2, 6 and then every 8 weeks) in RA patients with an inadequate response to DMARD's. To build the model, the price per unit paid by the government Hospitals was considered, taking into account the annual total therapy cost. Results on efficacy measures from published clinical trials considering an ACR 70 criteria (change from the basal in 70% of the ACR parameters) was used in the estimation of the incremental cost-effectiveness ratio (ICER). Other costs included in the model were obtained by the declared public budget of those Hospitals. RESULTS The annual total therapy cost for etanercept, adalimumab and infliximab per patient was $141,050, $158,938 and $163,152 Mexican pesos, respectively. The ACR 70 rates responses of etanercept, adalimumab and infliximab, indicated in clinical trials are 43%, 21% and 10% respectively. The ICER per additional patient achieving ACR 70 response of etanercept when compared with adalimumab was -$81,309, and -$66,976 when compared with infliximab etanercept was a dominant alternative compared with adalimumab and infliximab. CONCLUSIONS According to published results, the use of etanercept in patients with RA is the most cost-saving alternative. If the use of etanercept is increased, more patients could have access to biologic therapy and the health care institutions in Mexico could contain costs in the treatment of RA.