Abstract Background: Laparoscopic cholecystectomy at standard-pressure pneumoperitoneum uses a pressure of 12-14mm Hg, which may cause a variety of adverse physiological changes reflected as subclinical abnormalities in biochemical param-eters. The use of low-pressure pneumoperitoneum in the range of 8-10mm Hg has been shown to reduce the adverse physio-logical changes without affecting the outcome of surgery. Aim of Study: To study the effect of different levels of carbon dioxide pneumoperitoneum and duration of surgery on liver enzymes during laparoscopic cholecystectomy. Subjects and Methods: This study was done in a rand-omized controlled manner. Patients with gallstone disease (n=51) underwent laparoscopic cholecystectomy. Patients were randomly assigned to high-pressure laparoscopic chole-cystectomy (HPLC) (n=26) and low-pressure laparoscopic cholecystectomy (LPLC) (n=25). Liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were obtained preoperatively and on postoperative Days 1 and 7. Results: The two study groups had similar demographic profiles, and there were no significant differences in the operative time (HPLC, 45.654±4.088 minutes; LPLC, 47.32 ±2.81 minutes; p=0.096) and pneumoperitoneum time (HPLC, 33.923±3.212 minutes; LPLC, 32.440±3.874 minutes; p= 0.142). On postoperative Day 1, AST levels were 42.46±  13.27IU/L and 35±7.08 for HPLC and LPLC (p=0.016), respectively and ALT levels were 45.88±11.12IU/L and 38.48±9.908IU/L (p=0.016), respectively. Thus, liver enzyme activities were significantly elevated in the HPLC group compared with the LPLC group. Conclusions: LPLC causes less abnormality in enzymes in the postoperative period compared with HPLC. The distur-bances after the procedure are self-limited and not associated with any morbidity in patients with normal liver function tests.