OBJECTIVES: Fixed combinations of inhaled corticosteroids and long-acting β2-agonists are widely used in treatment of patients with chronic obstructive pulmonary disease (COPD) to reduce exacerbations. Cost-effectiveness analyses comparing the costs and effects of the fixed combinations budesonide/formoterol and fluticasone/salmeterol in COPD are scarce. The objective of this study was to evaluate the cost-effectiveness of budesonide/formoterol relative to fluticasone/salmeterol based on up to eleven years of real-world effectiveness data (NCT01146392) from a Swedish healthcare perspective. METHODS: Resource use and effectiveness data were collected retrospectively from primary care medical records’ data, patients ≥18 years, both sexes, with a diagnosis of COPD (J44) and merged with Swedish hospital, drug, and cause of death register data from 1 January 1999 to 31 December 2009.  Propensity score matching of treatment groups was done at the index date (first prescription of fixed combination post COPD diagnosis). Exacerbations were defined as hospitalisations and emergency room visits for COPD, prescription of glucocorticosteroids and/or prescription of antibiotics for respiratory tract infections. Annual exacerbation rates were calculated using Poisson regression. The effectiveness variable was the number of exacerbations avoided. Direct costs were calculated by applying year 2010 Swedish unit costs to the annual resource use. Bootstrapping was used to quantify uncertainty around estimates. RESULTS: Based on 2734 patients in each treatment group, the annual exacerbation rate was 0.800 for patients treated with budesonide/formoterol and 1.090 for patients treated with fluticasone/salmeterol (26.6% reduction, p<0.0001). Treatment with budesonide/formoterol was found to be cost-saving compared with treatment with fluticasone/salmeterol (total average annual per patient cost of SEK12 580 [€1318] and SEK15 979 [€1675], respectively). CONCLUSIONS: Budesonide/formoterol was the dominant strategy (more effective at lower cost) compared to fluticasone/salmeterol for the treatment of patients with COPD based on 11 years of real-world effectiveness data.