OBJECTIVES:  To estimate the cost-effectiveness of abatacept in combination with methotrexate (MTX) versus rituximab or tocilizumab in combination with MTX, in patients with Rheumatoid Arthritis with inadequate response to methotrexate (IR-MTX) in Chile. METHODS: Adapting a previously validated model, dynamic simulation techniques and clinical data from published literature were used to compare the clinical events, quality of life, and direct medical costs of abatacept, rituximab and tocilizumab. Costs of drug acquisition, administration and monitoring were considered. Costs were expressed in US Dollars of 2012 (Exchange rate: $ 487.8 Chilean pesos = 1 US Dollar). A 5-year time horizon for a cohort of 1000 patients and the payer’s perspective were assumed. Costs and health outcomes were discounted at 6% annually. Univariate sensitivity analysis was performed to assess the robustness of the model results. RESULTS: A hypothetical cohort of 1,000 patients with RA and IR-MTX in Chile, followed for 5 years, resulted in mean drug costs of: US$40,792, US$21,952, and US$35,849, for abatacept, rituximab and tocilizumab, respectively. Total direct medical costs (discounted) per patient were US$47,533 (46,510- 48,848) for abatacept, US$27,428 (27,017-27,914) for rituximab, and US$ 42,543 (41,545- 44,428) for tocilizumab. The total QALYs gained (discounted) by abatacept, rituximab and tocilizumab during the same period were: 2.06 (2.01-2.10), 1.11 (1.07-1.16) and 1.93 (1.87-1.97) respectively. The calculated Incremental Cost-Effectiveness Ratio (ICER) for abatacept compared to rituximab and tocilizumab were US$21,117 (18,089-25,792) and US$37,614 (9,179-185,253) per QALY gained, respectively. Sensitivity analysis confirmed the robustness of the model findings.  CONCLUSIONS: In Chile, according to the model inputs, abatacept showed better effectiveness in terms of QALYs than rituximab or tocilizumab, for patients with rheumatoid arthritis after an inadequate response to MTX. The results suggest that abatacept is cost-effective compared to rituximab (ICER ≤ 3 GDP per capita).