Changes in end-expiratory lung volume (∆EELV) in response to changes in PEEP (∆PEEP) have not been reported in mechanically ventilated patients with ARDS. The purpose of this study was to determine the utility of measurements of ∆EELV in determining optimal PEEP in ARDS patients. Nine patients with ARDS were prospectively recruited. ∆EELV was measured using magnetometers during serial decremental PEEP trials. Changes in PaO2 (∆PaO2) were simultaneously measured. Static respiratory system compliance (CRS), ∆PaO2/∆PEEP, and ∆EELV/∆PEEP were calculated at each level of PEEP. For the group, ∆EELV decreased by 1.09 ± 0.13 L (mean ± SD) as PEEP was reduced from 20 to 0 cm H2O with the greatest changes in ∆EELV occurring over the mid range of the decremental PEEP curve. Optimal values for CRS, ∆EELV/∆PEEP, and ∆PaO2/∆PEEP could be identified for each patient and occurred at PEEP levels ranging from 10 to 17.5 cm H2O. There was a significant correlation (r = 0.712, p = 0.047) between ∆PaO2/∆PEEP and ∆EELV/∆PEEP. ∆EELV can be measured from a decremental PEEP curve. Since ∆EELV is highly correlated with ∆PaO2, measures of ∆PaO2/∆PEEP may provide a surrogate for measures of ∆EELV/∆PEEP. Combining measures of ∆EELV/∆PEEP with measures of CRS may provide a novel means of determining optimal PEEP in patients with ARDS.