We report findings from a phase 3 trial evaluating the effects of mometasone furoate/formoterol (MF/F), administered via metered-dose inhaler, on pulmonary function in moderate-very severe COPD. This 26-wk, multicenter, randomized, double-blind, placebo (PBO)-controlled trial evaluated MF/F 400/10μg twice daily (BID) and 200/10μg BID in current/ex-smokers (≥10 pack-y) ages ≥40y with moderate−very severe COPD (mean baseline [BL] % predicted FEV1, 38.7%). Subjects received BID treatment with MF/F 400/10μg, MF/F 200/10μg, MF 400μg, F 10μg, or PBO. Lung function was analyzed for mean changes from BL in FEV1 over 0−12hrs (AUC0−12 FEV1) and pre-dose AM FEV1 at endpoint (EP) after 13wks or 26wks of treatment. 1193 subjects received treatment. At 13wks, changes from BL in AUC0−12 FEV1 with MF/F 400/10μg, MF/F 200/10μg, MF 400μg, F 10μg, PBO were 179mL,*†‡ 139mL,*† 53mL, 92mL,* 18mL, respectively (*P≤.004 vs PBO; †P≤.001 vs MF 400μg ‡P≤.001 vs F 10μg). At 26wks, changes from BL in AUC0−12 FEV1 with MF/F 400/10μg, MF/F 200/10μg, MF 400μg, F 10μg, PBO were 152mL,*† 120mL,*‡ 33mL, 63mL,§ 8mL, respectively (*P<.001 vs PBO; †P≤.001 vs MF 400μg, F 10μg; ‡P≤.027 vs MF 400μg, F 10μg; §P=.038 vs PBO). At 26wks, changes from BL in pre-dose AM FEV1 with MF/F 400/10μg, MF/F 200/10μg, MF 400μg, F 10μg, PBO were 92mL,*† 69mL,* 27mL, 10mL, 3mL (*P≤.030 vs PBO, F 10μg; †P=.017 vs MF 400μg). No unexpected AEs were observed; MF/F was generally well tolerated. MF/F treatments significantly improved lung function and were well tolerated in subjects with moderate to very severe COPD.