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This systematic review aimed to investigate: (a) the impact of laparoscopic surgery on oxidative stress (OS) and (b) the effect of laparoscopic surgery on OS in comparison with open surgery. Eligible trials were clinical trials or retrospective studies with at least 1 arm for laparoscopic surgery with measurements of at least 1 marker of OS or of antioxidant defenses. Twenty-nine trials fulfilled inclusion criteria. There was a great heterogeneity on measured OS markers, methods, and time periods of measurement and on the type of investigated operations. Methodological issues were raised including heterogeneity on study design, lack of reliability, low sensitivity, low specificity of the applied assays, and the limitations of the statistical methods. However, results were highly discordant with some studies suggesting less pronounced OS after laparoscopic surgery, other studies suggesting potentiation of OS after laparoscopic surgery and some studies demonstrating no difference in OS between open and laparoscopic surgery.