Background: A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F. Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 second (FEV 1 ) over 0–12 hours (AUC 0–12 FEV 1 ) with MF/F versus MF, and in morning predose FEV 1 with MF/F versus F. Key secondary endpoints were quality of life (Saint George’s Respiratory Questionnaire [SGRQ]), symptom-free nights, and partly stable COPD at 26 weeks, as well as time to first COPD exacerbation. Results: Significant improvements in FEV 1 AUC 0–12 occurred at endpoint with MF/F 400/10 and MF/F 200/10 versus MF 400 ( P ≤ 0.007). Significant bronchodilation occurred in 5 minutes with MF/F, and serial spirometry demonstrated sustained FEV 1 improvements with MF/F over the treatment period. Significant improvements in morning predose FEV 1 occurred with both MF/F doses, and these effects were further investigated by excluding results for subjects whose morning FEV 1 data were collected >2 days after the last dose of study treatment. Improvements in SGRQ total scores surpassed the minimum clinically important difference of at least 4 units with MF/F 400/10. MF/F 400/10 significantly reduced the time-to-first COPD exacerbation. Similar proportions of subjects in all five treatment groups reported treatment-emergent adverse events. Rates of pneumonia were low (≤1.0%) across treatment groups. Conclusion: MF/F 400/10 µg twice daily was shown to be an effective therapy for patients with moderate to very severe COPD, and both MF/F 400/10 µg twice daily and MF/F 200/10 µg twice daily were well tolerated. Keywords: chronic obstructive pulmonary disease, FEV 1 , spirometry, exacerbation, inhaled corticosteroid, bronchodilator Corrigendum for this paper has been published