Background: the laparoscopic cholecystectomy (LC), one of the utmost commonly assumed operations in general surgery. Adequate working space inside the abdominal cavity is required. Carbon dioxide (CO2) is used with a definite pressure to establish this working space. Aim: our study was to compare the hemodynamic symptoms, post-operative shoulder-tip pain and the frequency of nausea and vomiting between standard and low-pressure CO2 pneumoperitoneum (PP) in patients undergoing LC. Patients and Methods: a prospective randomized study was done on 50 patients aged 18 to 75 years in Bab ElShaaria hospital, Al-Azhar University with symptomatic gallstones. Patients were allocated into two groups: standard pressure (Group A: 12-14 mmHg) and low-pressure (Group B: 8-10 mmHg). Hemodynamics were assessed pre insufflation and 15 min post insufflation and desufflation. The frequency of nausea and vomiting were assessed at 0, 8, 16, 24-hour post-operative. Post-operative shoulder- tip was assessed 1, 6, 12, 24-hour post-operative. Statistical analysis was postulated using SPSS V.25. Results: a noticeable difference between the two groups was observed with respect to the mean systolic blood pressure (p=0.003) and the mean heart rate (p=0.001). Furthermore, a significant difference as regard post-operative shouldertip pain, which was higher in the standard pressure group (p< 0.05). There were no major differences between the two groups concerning the frequency of nausea and vomiting. Conclusion: low-pressure PP can be used instead of standard pressure considering its low side effects without any effect on the working space and quality of the surgical procedure.