ObjectiveTo determine whether positive end-expiratory pressure (PEEP) and prone position present a synergistic effect on oxygenation and if the effect of PEEP is related to computed tomography scan lung characteristic.DesignProspective randomized study.SettingFrench medical intensive care unit.PatientsTwenty-five patients with acute respiratory distress syndrome.InterventionsAfter a computed tomography scan was obtained, measurements were performed in all patients at four different PEEP levels (0, 5, 10, and 15 cm H2O) applied in random order in both supine and prone positions.Measurements and Main ResultsAnalysis of variance showed that PEEP (p< .001) and prone position (p< .001) improved oxygenation, whereas the type of infiltrates did not influence oxygenation. PEEP and prone position presented an additive effect on oxygenation. Patients presenting diffuse infiltrates exhibited an increase of Pao2/Fio2related to PEEP whatever the position, whereas patients presenting localized infiltrates did not have improved oxygenation status when PEEP was increased in both positions. Prone position (p< .001) and PEEP (p< .001) reduced the true pulmonary shunt. Analysis of variance showed that prone position (p< .001) and PEEP (p< .001) reduced the true pulmonary shunt. The decrease of the shunt related to PEEP was more pronounced in patients presenting diffuse infiltrates. A lower inflection point was identified in 22 patients (88%) in both supine and prone positions. There was no difference in mean lower inflection point value between the supine and the prone positions (8.8 ± 2.7 cm H2O vs. 8.4 ± 3.4 cm H2O, respectively).ConclusionsPEEP and prone positioning present additive effects. The prone position, not PEEP, improves oxygenation in patients with acute respiratory distress syndrome with localized infiltrates.