Background: Lung protective ventilation during the intraoperative period is now well established. However, the additional role of positive end-expiratory pressure (PEEP) during the intraoperative period remains uncertain in major laparoscopic gynecological surgery. The authors hypothesized that compliance-based optimum PEEP titration reduces postoperative lung atelectasis and improves outcomes.Methods: Patients undergoing major laparoscopic pelvic gynecological surgeries with healthy lungs were randomized to the fixed PEEP group (PEEP 5 cm H2O and recruitment maneuver {RM}) and optimum PEEP group (compliance-based PEEP and RM). Lung ultrasound and arterial blood gas analysis were performed at four time points. Modified lung ultrasound scoring was done, and the same was used as means of assessing lung aeration and the amount of lung atelectasis. Postoperative supplemental oxygen requirement and duration were also assessed and compared.Results: Lung ultrasound score (LUS) 30 minutes after extubation in fixed (Group F) and optimum (Group O) PEEP groups were median (interquartile range {IQR}) 3 (2-3) versus 1 (1-2), p=0.0001. Ventilatory parameters between Group F and Group O after lung recruitment were tidal volume (mean 357 mL {SD: 35} versus 362 mL {SD: 22}, p=0.46), PEEP (median, 5 cm H2O {IQR: 5-5} versus median 16 cm H2O {IQR: 14-18}), peak airway pressure (median 26 cm H2O {IQR: 24-28} versus median 30 cm H2O {IQR: 28-32} p<0.0001), plateau pressure (median 22 cm H2O {IQR: 20-24} versus median 26 cm H2O {IQR: 24-28} p<0.0001), static compliance (32.07±8.36 mL cm H2O-1 versus 39.58±8.99 mL cm H2O-1, p=0.0002). The number of patients requiring postoperative oxygen therapy to maintain SpO2>94% after extubation in postanesthesia care unit (PACU) was statistically significantly greater in group F (39/41 {95%} versus 30/41 {73%}, p=0.007). Median (IQR) duration of oxygenation therapy in the first 24 hours of the postoperative period between Group F and Group O differed with statistical significance, with the median (IQR) values being 25 (20-30) minutes versus 10 (0-15) minutes (p<0.0001).Conclusions: The modified lung ultrasound score significantly differed intraoperatively between the two groups, with lower scores in the optimum PEEP group. This has reflected improved postoperative outcomes in optimum PEEP group patients, with fewer patients requiring postoperative oxygen supplementation and reduced supplemental oxygen requirement duration.