The mechanisms for symptomatic improvement following lung volume reduction surgery for emphysema are poorly understood. We hypothesized that enhanced neuromechanical coupling of the diaphragm is an important factor in this improvement. We studied seven patients with diffuse emphysema before and 3 mo after surgery. Patients showed improvements in 6-min walking distance (p = 0.002) and dyspnea (p = 0.04). The pressure output of the respiratory muscles, quantified as pressure-time product per minute (PTP/min), decreased after surgery (p = 0.03), as did PaCO2 (p = 0.02). Maximal transdiaphragmatic pressures (Pdi(max)) increased from 80.3 +/- 9.5 (SE) to 110.8 +/- 9.3 cm H2O after surgery (p = 0.03), and the twitch transdiaphragmatic pressure response to phrenic nerve stimulation (Pdi(tw)) increased from 17.2 +/- 2.4 to 25.9 +/- 3.0 cm H2O (p = 0.02); these increases were greater than could be accounted for by a decrease in lung volume. The contribution of the diaphragm to tidal breathing, assessed by relative changes in gastric and transdiaphragmatic pressures, increased after surgery (p = 0.008). Net diaphragmatic neuromechanical coupling, quantified as the quotient of tidal volume (normalized to total lung capacity) to tidal change in Pdi (normalized to Pdi(max)), improved after surgery (p = 0.03) and was related to the increase in 6-min walking distance (r = 0.86, p = 0.03) and decrease in dyspnea (r = 0.76, p = 0.08). In conclusion, lung volume reduction surgery effects an improvement in diaphragmatic function, greater than can be accounted for by a decrease in operating lung volume, and enhances diaphragmatic neuromechanical coupling.