Background: Low pressure laparoscopic cholecystectomy has been advocated due to reduction in postoperative pain, ventilation problems, hemodynamic complications, and potential for reduction in surgical events. No reported data have been found focusing on the effects of low-pressure laparoscopic cholecystectomy on intracranial pressure (ICP). The aim of this study was to investigate the effect of low-pressure laparoscopic cholecystectomy on intracranial pressure measured by optic nerve sheath diameter (ONSD) in Imam Hossein Medical Center, Tehran, Iran. Methods: The patients classified as American Society of Anesthesiologists physical status I or II undergoing elective laparoscopic cholecystectomy due to benign gallbladder disease were randomly assigned to low-pressure laparoscopy (LPL) group or normal pressure laparoscopy group (NPL). ONSD was measured at 3 different times: (1) before induction of anesthesia; (2) after initiation of gas insufflation; and (3) after the termination of gas insufflation. The collected data were entered into SPSS software (V 24). Data were demonstrated with frequency (percentage) or mean ± standard deviation. We used the Mann-Whitney test to compare the means of continuous variables. The Friedman test was used to compare the mean of variables over time in each of the 2 groups. The significance level in all analyses was considered at ˂0.05. Results: ONSD after the termination of gas insufflation was significantly lower in the LPL group with the mean of 4.97±0.83 mm than the NPL group with the mean of 5.62±1.32 mm (p=0.018). ONSD before induction of anesthesia or immediately after gas insufflation did not differ significantly between LPL and NPL groups. Duration of anesthesia and surgery, mean arterial pressure, the total dose of propofol (p=0.600), and fentanyl (p=0.201) did not show significant differences between the 2 groups. Conclusion: ONSD was lower with low-pressure laparoscopic cholecystectomy after the termination of gas insufflation, which emphasized the neural protective effect of low intraperitoneal pressure. Further studies are needed to evaluate this diagnostic tool in different populations, especially in patients with increased ICP undergoing laparoscopic interventions.