Purpose Intra-abdominal hypertension (IAH) is associated with impaired respiratory function. Animal data suggest that positive end-expiratory pressure (PEEP) levels adjusted to intra-abdominal pressure (IAP) levels may counteract IAH-induced respiratory dysfunction. In this pilot study, our aim was to assess whether PEEP adjusted for IAP can be applied safely in patients with IAH. Materials and methods We included patients on mechanical ventilation and with IAH. Patients were excluded with severe cardiovascular dysfunction or severe hypoxemia or if the patient was in imminent danger of dying. Following a recruitment manoeuvre, the following PEEP levels were randomly applied: PEEP of 5 cmH2O (baseline), PEEP = 50% of IAP, and PEEP = 100% of IAP. After a 30 min equilibration period we measured arterial blood gases and cardio-respiratory parameters. Results Fifteen patients were enrolled. Six (41%) patients did not tolerate PEEP = 100% IAP due to hypoxemia, hypotension or endotracheal cuff leak. PaO2/FiO2 ratios were 234 (68), 271 (99), and 329 (107) respectively. The differences were significant (p = 0.009) only between baseline and PEEP = 100% IAP. Conclusions PEEP = 100% of IAP was not well-tolerated and only marginally improved oxygenation in ventilated patients with IAH.