Background: Surgical injury is associated with oxidative stress, often due to ischemia/reperfusion injury. During laparoscopy, increased intra-abdominal pressure caused by pneumoperitoneum may cause splanchnic ischemia followed by reperfusion due to deflation. We measured several markers of oxidative stress in patients undergoing laparoscopic cholecystectomy (LC) versus open cholecystectomy (OC) to find if these surgical procedures result in different patterns of oxidative stress. Methods: This prospective study enrolled 43 patients with symptomatic cholelithiasis, of whom 21 underwent open, and 22 laparoscopic, cholecystectomy. Twenty healthy adults comprised the control group. Total antioxidant status (TAS), superoxide dismutase (SOD), endogenous peroxide level (POX), oxidized low density lipoprotein (oLDL) autoantibodies (oLAb), and neopterin were measured preoperatively and on postoperative days 1, 3, and 7. Results: POX values decreased significantly on postoperative day 1 in the OC (P<0.01), but not in the LC, group. On postoperative day 7, POX values were higher than preoperatively in both groups (P<0.01) with no difference between the LC and OC groups. Significant postoperative elevations of oLAb and neopterin levels were observed only on postoperative day 7 in the OC group. There were no changes of oLAb and neopterin levels in the LC group. TAS and SOD levels did not change after either LC or OC. Conclusion: Cholecystectomy, either open or laparoscopic, caused only moderate oxidative stress. Open cholecystectomy caused changes of oLAb and neopterin, suggesting more severe oxidative stress, and a possible role of reactive oxygen species in the healing of the laparotomic wound.