ObjectiveTo test the hypothesis that helium/oxygen mixture can reduce the work of breathing at the end of the weaning process in patients with chronic obstructive pulmonary disease.DesignProspective, randomized, crossover study.SettingTwo medical intensive care units at two university tertiary care centers.PatientsThirteen patients with chronic obstructive pulmonary disease evaluated just before and after extubation.InterventionsHelium/oxygen and air/oxygen mixtures were administered sequentially, for 20 mins each, in a randomized order, just before extubation. It was possible to repeat the study after extubation in five patients.Measurements and Main ResultsBefore extubation, the helium/oxygen mixture induced no significant variation in the breathing pattern. By contrast, it reduced the work of breathing from 1.442 ± 0.718 J/L (mean ± sd) to 1.133 ± 0.500 J/L (p< .05). This reduction was explained mainly by a reduction in the resistive component of the work of breathing from 0.662 ± 0.376 to 0.459 ± 0.256 J/L (p< .01). We also observed a slight reduction in the intrinsic positive end-expiratory pressure from 2.9 ± 2.1 cm H2O to 2.1 ± 1.8 cm H2O (p< .05). Similar results were also observed after extubation in five patients in whom the repetition of the study was possible.ConclusionsIn spontaneously breathing intubated patients with chronic obstructive pulmonary disease recovering from an acute exacerbation, helium/oxygen mixture reduces the work of breathing as well as intrinsic positive end-expiratory pressure without modifying the breathing pattern.