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Background: A peak inspiratory flow rate (PIFR) of <60 L/min against the internal resistance (resist) of a dry powder inhaler (DPI) may limit the ability of a patient with chronic obstructive pulmonary disease (COPD) to achieve bronchodilation. The hypothesis was that lung function would be higher with a beta-agonist inhaled via nebulization compared with dry powder in patients with COPD who exhibit a PIFRresist of <60 L/min against the Diskus(®)., Methods: This study was randomized, single-blind, and crossover with spirometry and inspiratory capacity (IC) measured at 15, 30, and 120 min post treatment. The efficacy of arformoterol aerosol solution (15 μg/2 mL) via nebulizer was compared with salmeterol dry powder (50 μg) via Diskus. The primary outcome was the change in lung function from baseline at 2 hr as these two inhaled beta-agonists have the similar peak bronchodilator effect as measured by forced expiratory volume in 1 sec (FEV1)., Results: Twenty patients (15 females/5 males) with postalbuterol FEV1 of 0.83±0.31 L (38±12% predicted) and PIFRresist of 53±5 L/min completed the study. At 15 min, improvements in FEV1, forced vital capacity (FVC), and IC were significantly higher with arformoterol than with salmeterol. At 2 hr, changes in FVC and IC, but not FEV1, were significantly higher with arformoterol. At visit 3, patient preference was similar for salmeterol Diskus (n=8) and arformoterol solution (n=7), whereas five patients reported no preference., Conclusions: At peak effect (2 hr), volume responses were greater with arfomoterol via nebulizer compared with dry powder salmeterol in patients with COPD who had a PIFRresist of <60 L/min. Bronchodilator therapy via nebulization should be considered in patients with COPD who have a suboptimal PIFRresist against a particular DPI.