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Low tidal volume ventilation with low PEEP during surgery may induce lung inflammation. BACKGROUND: Compared to conventional tidal volume ventilation, low tidal-volume ventilation reduces mortality in cased of acute respiratory distress syndrome. The aim of the present study is to determine whether low tidal-volume ventilation reduces the production of inflammatory mediators in the lungs and improves physiological status during hepatic surgery. METHODS: We randomly assigned patients undergoing hepatectomy into 2 groups: conventional tidal-volume vs. low tidal-volume (12 vs. 6 mL•kg(-1) ideal body weight) ventilation with a positive end-expiratory pressure of 3 cm H2O. Arterial blood and airway epithelial lining fluid were sampled immediately after intubation and every 3 h thereafter. RESULTS: Twenty-five patients were analyzed. No significant changes were found in hemodynamics or acid-base status during the study. Interleukin-8 was significantly elevated in epithelial lining fluid from the low tidal-volume group. Oxygenation evaluated immediately after admission to the post-surgical care unit was significantly worse in the low tidal-volume group. CONCLUSIONS: Low tidal-volume ventilation with low positive end-expiratory pressure may lead to pulmonary inflammation during major surgery such as hepatectomy. TRIAL REGISTRATION: The effect of ventilatory tidal volume on lung injury during hepatectomy that requires transient liver blood flow interruption. UMIN000021371 (03/07/2016); retrospectively registered.