Objective: Abatacept is a new selective co-stimulation modulator recently approved in Brazil for the treatment of patients with moderately to severely active rheumatoid arthritis (RA) and inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). We estimated the cost-effectiveness of Abatacept in patients with inadequate response to Methotrexate. Methods: We developed a Markov simulation model to depict progression of functional disability over time in patients with moderately to severely active RA and inadequate response to MTX. Functional disability was expressed in terms of the Health Assessment Questionnaire Disability Index (HAQ-DI). Patients were assumed to receive weekly pulse MTX alone or weekly pulse MTX plus abatacept administered on days 1, 14, and 29, and every 4 weeks thereafter. Costs with drug acquisition, administration and monitoring were considered. Estimations used data from a Phase III clinical trial of abatacept in patients with inadequate response to MTX (AIM] plus secondary data sources. Cost-effectiveness of abatacept was expressed in terms of the incremental cost (2006 Brazil R$) per quality-adjusted life-year (QALY) gained versus MTX therapy alone; lifetime horizons was employed in the analyses. Costs and health effects were discounted at 3% annually. Results: Over the lifetime, abatacept therapy was estimated to yield an average of 1.61 additional QALYs per patient (vs. MTX alone) at a mean incremental cost of R$146.095/QALY (US$83,483, US$1=R$1.75). Conclusion: Abatacept presented the best cost-effectiveness ratio vis-à-vis etanercept, adalimumab, and infliximab, with its incremental costs of R$202.581/QALY, R$189.100/QALY and R$236.479/QALY, respectively vs. Methrotexate alone.