Abstract : The place of combinations of bronchodilators (longacting beta-agonist / muscarinic agonist or LABA / LAMA) in the prevention of the exacerbations of the chronic obstructive pulmonary disease (COPD) is not still clearly established, and need a comparison with combination of LABA/ inhaled steroids. FLAME was a randomized non-inferiority phase 3 study comparing indacaterol/glycopyrronium 110/50 μg (IND/GLY) once daily with salmeterol/proprionate of fluticasone 50/500 μg (SAL/FC) twice daily. The primary objective of the study was to demonstrate that IND/GLY was non-inferior to SAL/FC in terms of reduction of all COPD exacerbations (mild/moderate/severe) during 52 weeks of treatment in patients having had at least 1 exacerbation in previous 12 months. The combination IND/GLY showed not only non inferiority, but also superiority, to SAL/FC in reducing the annual rate of all COPD exacerbations (mild, moderate, or severe) by 11 % by comparison with SAL/FC (p = 0.003), and by 17 % for the annual rate of moderate or severe exacerbations (p inferior to 0.001). IND/GLY prolonged the time to the first COPD exacerbation by 16 % for mild, 22 % for moderate and 19 % for severe by comparison with SAL/FC (all with p inferior to 0.05). FLAME study showed that IND/GLY, a steroid-free option, is more effective than SAL/FC in preventing COPD exacerbations in patients with one or more exacerbations in the past year.