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Introduction Several dual bronchodilator fixed-dose inhaler medications were recently approved for the treatment of chronic obstructive pulmonary disease (COPD). These products combine a long-acting β2-agonist (LABA) and long-acting muscarinic antagonist (LAMA). In clinical trials, the separate mechanisms of the bronchodilators resulted in improved lung function. COPD treatment guidelines currently recommend combination LABA/LAMA as alternative therapy to combination LABA/inhaled corticosteroid (ICS). Evidence is limited on the comparative effectiveness of LABA/LAMA and LABA/ICS in COPD. The objective of this study was to compare real-world COPD exacerbation rates among patients treated with LABA/LAMA with those treated with LABA/ICS. Methods This was a retrospective observational study of COPD patients in the United States treated with LABA/LAMA or LABA/ICS combination. Insurance claims from January 1, 2004, through December 31, 2014, were used as the data source. Patients were required to have greater than one prescription filled for the combination medications, and they were followed from 30 days after drug initiation. Individuals were censored if they discontinued a study medication, initiated medication from the opposite cohort (LAMA or ICS), lost enrollment eligibility, or at the study period end. Exacerbation rates were compared using Poisson regression. Results There were 5384 patients in the LABA/LAMA cohort and 473,388 patients in the LABA/ICS cohort. The LABA/LAMA cohort was older, had more comorbidities, and more severe COPD. Unadjusted annual exacerbation rates were 2.87 events per person-year (standard deviation [SD] 5.14) in the LABA/LAMA cohort and 1.68 (SD 9.82) in the LABA/ICS cohort. The adjusted incidence rate ratio was 0.98 (95% confidence interval 0.95-1.01) for LABA/LAMA compared with LABA/ICS. Conclusions The LABA/LAMA combination had similar effectiveness to LABA/ICS as measured by exacerbation rates in COPD patients. As a result, characteristics other than effectiveness, such as symptom control, cost, patient preferences, and adverse events, may be important in selecting between the two regimens. [ABSTRACT FROM AUTHOR]