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There is no ideal method for determination of positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) patients. We compared the effects of end-expiratory lung volume (EELV)-guided versus PaO 2 -guided PEEP determination on respiratory mechanics and oxygenation during the first 48 hours in moderate to severe ARDS. Twenty-two patients with moderate to severe ARDS admitted to an academic medical ICU were assigned to PaO 2 -guided ( n  = 11) or to EELV-guided PEEP determination ( n  = 11) group. First, an incremental PEEP trial was performed by increasing PEEP by 3 cmH 2 O steps from 8 to 20 cmH 2 O and in each step EELV and lung mechanics were measured in both groups. Then, oxygenation and respiratory mechanics were measured under the determined PEEP at 4, 12, 24, and 48th hours. After the incremental PEEP trial, over the 48 hours of the study period, in the EELV-guided group PaO 2  and PaO 2 /FiO 2  increased ( p  = 0.04 and  p  = 0.02; respectively), whereas they did not change in PaO 2 -guided group ( p  = 0.09 and  p  = 0.27; respectively). In all patients, the median value of EELV change (ΔEELV) during incremental PEEP trial was 25%. In patients with ΔEELV &gt; 25% ( n  = 11) PaO 2 , PaO 2 /FiO 2  and Cs increased over time in 48 hours ( p  = 0.03,  p  &lt; 0.01, and  p  = 0.04; respectively), whereas they did not change in those with ΔEELV ≤ 25% ( n  = 11) ( p  = 0.73,  p  = 0.51, and  p  = 0.73; respectively). Compared to PaO 2 -guided PEEP determination, EELV-guided PEEP determination resulted in greater improvement in oxygenation over time. Patients who had &gt; 25% improvement in EELV during a PEEP trial had greater improvement in oxygenation and compliance over 48 hours. Supplemental data for this article is available online at

Effects of end-expiratory lung volume versus PaO 2 guided PEEP determination on respiratory mechanics and oxygenation in moderate to severe ARDS