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Acute respiratory distress syndrome is characterized by collapse of gravitationally dependent lung regions that usually diverts tidal ventilation toward nondependent regions. We hypothesized that higher positive end-expiratory pressure and enhanced spontaneous breathing may increase the proportion of tidal ventilation reaching dependent lung regions in patients with acute respiratory distress syndrome undergoing pressure support ventilation.Prospective, randomized, cross-over study.General and neurosurgical ICUs of a single university-affiliated hospital.We enrolled ten intubated patients recovering from acute respiratory distress syndrome, after clinical switch from controlled ventilation to pressure support ventilation.We compared, at the same pressure support ventilation level, a lower positive end-expiratory pressure (i.e., clinical positive end-expiratory pressure = 7 ± 2 cm H2O) with a higher one, obtained by adding 5 cm H2O (12 ± 2 cm H2O). Furthermore, a pressure support ventilation level associated with increased respiratory drive (3 ± 2 cm H2O) was tested against resting pressure support ventilation (12 ± 3 cm H2O), at clinical positive end-expiratory pressure.During all study phases, we measured, by electrical impedance tomography, the proportion of tidal ventilation reaching dependent and nondependent lung regions (Vt%dep and Vt%nondep), regional tidal volumes (Vtdep and Vtnondep), and antero-posterior ventilation homogeneity (Vt%nondep/Vt%dep). We also collected ventilation variables and arterial blood gases. Application of higher positive end-expiratory pressure levels increased Vt%dep and Vtdep values and decreased Vt%nondep/Vt%dep ratio, as compared with lower positive end-expiratory pressure (p < 0.01). Similarly, during lower pressure support ventilation, Vt%dep increased, Vtnondep decreased, and Vtdep did not change, likely indicating a higher efficiency of posterior diaphragm that led to decreased Vt%nondep/Vt%dep (p < 0.01). Finally, PaO2/FIO2 ratios correlated with Vt%dep during all study phases (p < 0.05).In patients with acute respiratory distress syndrome undergoing pressure support ventilation, higher positive end-expiratory pressure and lower support levels increase the fraction of tidal ventilation reaching dependent lung regions, yielding more homogeneous ventilation and, possibly, better ventilation/perfusion coupling.