BACKGROUND: The first aim of this study was to evaluate the capacity of electrical impedance tomography (EIT) to identify the effect of PEEP on regional ventilation distribution and the regional risk of collapse, overdistention, hypoventilation, and pendelluft in mechanically ventilated patients. The second aim was to evaluate the feasibility of EIT for estimating airway opening pressure (AOP). METHODS: The EIT signal was recorded both during baseline cyclic ventilation and slow insufflation for one breath for 9 subjects with moderate-to-severe ARDS. From these data, the AOP and volumes insufflated to lung regions with or without the risk of either collapse, overdistention, hypoventilation, or pendelluft were assessed at 3 PEEP levels (5, 10, and 15 cm HO). PEEP levels were compared by Friedman analysis of variance and the AOP measured by EIT evaluated using an F-test and the Bland and Altman method. RESULTS: The volume for which there was no specific risk significantly decreased at the highest PEEP from 55 ± 31% tidal volume (V) at PEEP 5 or 82 ± 18% V at PEEP 10 to 10 ± 30% V at PEEP 15 ( = .038 between PEEP 5 vs PEEP 15; = .01 between PEEP 10 vs PEEP 15). The volume associated with overdistention significantly increased with increasing PEEP, whereas that associated with atelectrauma significantly decreased. Pendelluft significantly decreased with increasing PEEP: V of 8.9 ± 18.6%, 3.6 ± 7.0%, and 3.2 ± 7.1% for PEEP 5, PEEP 10, and PEEP 15, respectively. The center of ventilation tended to increase in the dependent direction with higher PEEP. The AOPs assessed by EIT and from the pressure-volume curve were in good agreement (bias 0.48 cm HO). CONCLUSIONS: Our results suggest that EIT could aid clinicians in making personalized and reasoned choices in setting the PEEP for subjects with ARDS.