Background: Respiratory system elastance (ERS) is an important determinant of the responsiveness of intracranial pressure (ICP) to positive end-expiratory pressure (PEEP). However, lung elastance (EL) and chest wall elastance (ECW) were not differentiated in previous studies. We tested the hypothesis that patients with high ECW or a high ECW/ERS ratio have greater ICP responsiveness to PEEP. Methods: An esophageal balloon catheter was placed to measure esophageal pressure. PEEP was increased from 5 to 15 cmH2O. Airway pressure and esophageal pressure were measured and EL, ECW and ERS were calculated at the two PEEP levels. Patients were classified into either an ICP responder group or a non-responder group based on whether the change of ICP after PEEP adjustment was greater than or less than the median of the overall study population. Results: The magnitude of the increase in esophageal pressure (median [interquartile range]) at end-expiratory occlusion was significantly increased in the responder group compared with that in the non-responder group (4.1 [2.7-4.1] versus 2.7 [0.0-2.7] cmH(2)O, p = 0.033) after PEEP adjustment. ECW and the ECW/ERS ratio were significantly higher in ICP responders than in non-responders at both low PEEP (p = 0.021 and 0.017) and high PEEP (p = 0.011 and 0.025) levels. No significant differences in ERS and EL were noted between the two groups at both PEEP levels. Conclusions: Patients with greater ICP responsiveness to increased PEEP exhibit higher ECW and a higher ECW/ERS ratio, suggesting the importance of ECW monitoring.