© 2021 Sociedade Brasileira de AnestesiologiaBackground: Positive end-expiratory pressure (PEEP) can overcome respiratory changes that occur during pneumoperitoneum application in laparoscopic procedures, but it can also increase intracranial pressure. We investigated PEEP vs. no PEEP application on ultrasound measurement of optic nerve sheath diameter (indirect measure of increased intracranial pressure) in laparoscopic cholecystectomy. Methods: Eighty ASA I–II patients aged between 18 and 60 years scheduled for elective laparoscopic cholecystectomy were included. The study was registered in the Australian New Zealand Clinical Trials (ACTRN12618000771257). Patients were randomly divided into either Group C (control, PEEP not applied), or Group P (PEEP applied at 10 cmH20). Optic nerve sheath diameter, hemodynamic, and respiratory parameters were recorded at six different time points. Ocular ultrasonography was used to measure optic nerve sheath diameter. Results: Peak pressure (PPeak) values were significantly higher in Group P after application of PEEP (p = 0.012). Mean respiratory rate was higher in Group C at all time points after application of pneumoperitoneum (p < 0.05). The mean values of optic nerve sheath diameters measured at all time points were similar between the groups (p > 0.05). The pulmonary dynamic compliance value was significantly higher in group P as long as PEEP was applied (p = 0.001). Conclusions: During laparoscopic cholecystectomy, application of 10 cmH2O PEEP did not induce a significant change in optic nerve sheath diameter (indirect indicator of intracranial pressure) compared to no PEEP application. It would appear that PEEP can be used safely to correct respiratory mechanics in cases of laparoscopic cholecystectomy, with no significant effect on optic nerve sheath diameter.