Background: Baseline high neuromuscular drive is present in chronic obstructive pulmonary disease (COPD). In moderate-to-very severe COPD patients, both static and/or dynamic pulmonary hyperinflation have been demonstrated at rest. Aim: To assess the influence of dynamic hyperinflation on neuromuscular drive at rest. Methods: We recruited 22 patients with severe-to-very severe COPD showing resting dynamic pulmonary hyperinflation, as assessed by the baseline reduction of inspiratory capacity (IC) (< 80% of predicted). IC, occlusion pressure (P-0.1), maximal inspiratory pressure (MIP), and their ratio were measured at end-expiratory lung volume (EELV) before and after acute inhalation of 400 mcg of albuterol (metered-dose inhaler plus spacer). In these patients the bronchodilator response was assessed also as lung volume changes. Results: Only in COPD patients with a marked increase in IC (> 12% of baseline and at least 200 mL) after bronchodilator, resting P-0.1 showed a clinically significant decrease, despite the EELV diminution (P < 0.001). MIP was augmented following EELV reduction and therefore the P-0.1/MIP ratio was markedly decreased (P < 0.001). In contrast, no changes in these indices were found after bronchodilator in COPD patients with insignificant variations of IC. Breathing pattern parameters did not vary in both sub-groups after albuterol. Conclusion: Following bronchodilator, significant P-0.1 decrease, MIP increase, and reduction of the P-0.1/MIP ratio were found only in COPD patients with a marked IC increase and these changes were closely related. These findings suggest that bronchodilators, by decreasing dynamic hyperinflation, may control exertional and/or chronic dyspnea partly through a reduction of central neuromuscular drive.