Postoperative pulmonary complications are common after cardiac surgery and have been related to lung collapsus during cardiopulmonary bypass (CPB). There is no consensus on the effects of maintaining mechanical ventilation during CPB to decrease these complications.To determine whether maintaining low-tidal ventilation (3 mL/kg 5 times per minute, with positive end expiratory pressure 5 cmH2O) during CPB (VENT strategy) was superior to a resting-lung strategy, with no ventilation (noV strategy), regarding postoperative pulmonary complications, including mortality.In a randomized controlled trial, patients undergoing cardiac surgery at a single center from May 2017 to August 2019 were randomized between VENT and noV strategy during CPB (1:1 ratio). Apart from CPB phase, perioperative ventilation procedures were standardized.The study included 1501 patients (68.8 ±10.3 years, 1152 (76.7%) men, EuroSCORE II 2.3 ±2.7). There were 756 patients in the VENT strategy group and there were no differences in baseline characteristics and types of procedures between the two groups. Intention-to-treat analysis yielded no significant difference between VENT and noV groups regarding incidence of the primary composite outcome combining death, early respiratory failure, ventilation support beyond day 2 and reintubation with 112/756, 14.8% in the VENT group versus 133/745, 17.9% in the noV group, odds-ratio(OR)=0.80 (95% confidence interval=0.61-1.05, p =0.11). Strict per-protocol analyses on 1338 (89.1%) patients with equally distributed preoperative characteristics yielded similar results (OR=0.81 (0.60-1.09), p=0.16). Post-hoc analysis on the subgroup of isolated coronary artery bypass graft (CABG) procedures (n=725), showed that VENT was superior to noV strategy regarding the primary outcome (OR=0.56 (0.37-0.84), p=0.005).Among patients undergoing cardiac surgery with CPB, continuation of low-tidal volume ventilation was not superior to no ventilation during CPB, with respect to postoperative complications, including death, early respiratory failure, ventilation support beyond day 2 and reintubation.