OBJECTIVES To determine the cost-effectiveness ratio for fluticasone/salmeterol combination in the treatment of Chronic Obstructive Pulmonary Disease - COPD, in Brazilian public sector. METHODS A cost-effectiveness analysis from the public payer perspective, with a time horizon of 5 years was conduct. A decision tree with a Markov chain considering the probabilities of increasing, decreasing or maintaining disease severity through four health states, three of them based on FEV1 from moderate to very severe according to American Thoracic Society (ATS) guidelines were performed. Study comparators examined were usual care (UC), long-acting anticholinergic drug, tiotropium (TIO) and fluticasone/salmeterol (SERETIDE®). The clinical aspects regarding benefits (exacerbations rates) and probabilities of transition data were extract from head to head randomized clinical trials for the alternatives. Treatment costs including maintenance costs on each stage of disease and moderate or severe exacerbations were collected from public payer reimbursement list and drugs costs were collected from Price Indexes – BPS or manufactures price list. The discounting rate was 5% for costs and benefits, the results were converted in US Dollars using a rate of R$2.3/USD 1.00. A one-way sensitivity analysis was performed. RESULTS Patients using fluticasone/salmeterol or tiotropium get more benefits compared with usual care (TIO=6.75; SERETIDE®=6.82 versus 7.61 exacerbation in 5 years), and usual care remains the lowest total cost per treatment (UC=USD1,519; SERETIDE®=US$3025 and TIO US$ 4840). The CE ratios were US$200; US$1904 and US$1649 for UC; SERETIDE® and TIO, respectively. The sensitivity analysis on efficiency and costs of fluticasone/salmeterol results show sensitivity to the price of tiotropium. CONCLUSIONS SERETIDE® is a cost-effective therapy for low level of willingness to pay; it offers the protection against exacerbations at low cost compared with TIO. Results are sensitive to TIO's price, showing the need of public policies to assure the best resource allocation.