Patients with chronic obstructive pulmonary disease (COPD) and suboptimal peak inspiratory flow rate (sPIFR) may not benefit optimally from dry powder inhalers (DPI) because of inadequate inspiratory flow. Nebulized bronchodilators may provide a better alternative. We compared bronchodilation with the long-acting muscarinic antagonist (LAMA) revefenacin for nebulization versus the DPI LAMA tiotropium, in patients with COPD and sPIFR (< 60 L/min against the resistance of Diskus®). This was a randomized, double-blind, double-dummy, 28-day Phase 3b study in patients with COPD enrolled based on sPIFR. The primary endpoint was trough forced expiratory volume in 1 second (FEV ) on Day 29 for revefenacin for nebulization versus tiotropium HandiHaler® DPI. We enrolled 206 patients with mean (standard deviation) age, 65 (8) years; percent predicted FEV , 37 (16)%; PIFR, 45 (12) L/min. In the intent-to-treat (ITT) population, revefenacin improved trough FEV from baseline; however, the difference versus tiotropium was not significant (least squares LS mean difference standard error, 17.0 22.4 mL, P=0.4461). In a prespecified analysis of patients with FEV < 50% predicted, revefenacin produced an LS mean difference (95% confidence interval CI), 49.1 (6.3-91.9) mL in trough FEV and 103.5 (7.7-199.3) mL in forced vital capacity versus tiotropium. Revefenacin produced >100 mL increase in FEV in 41.6% versus 34.4% of patients with tiotropium in ITT and 41.4% versus 25.7% of patients in FEV < 50% predicted populations. Revefenacin did not produce significant improvements in FEV1 versus tiotropium in the ITT population, but increased trough FEV in patients with FEV < 50% predicted and sPIFR. Clinical Trial Registration (www.Clinicaltrials.gov): Study 0149 (NCT03095456).