The purpose of our study was to evaluate the clinical impact of reperfusion injury after normothermic ischemia during major liver resections and the effect of an intraoperative antioxidant infusion. This prospective randomized study comprised 50 patients; half of them (treatment group) were given an antioxidant infusion containing tocopherol and ascorbate immediately prior to reperfusion onset. Venous blood samples for the determination of MDA-TBARS (malondialdehyde-thiobarbituric acid reactive substances) by a HPLC-based test as a marker of lipid peroxidation were taken prior to ischemia, 30 min after reperfusion onset and at the end of the operation. In the control group there was a significant increase of MDA-TBARS (p = 0.001) at 30 min after reperfusion onset. At the end of the operation the values had returned to the initial level. The treatment group showed only a marginal increase (p-value for the difference between the two groups: 0.007). After exclusion of the patients with histologically proven advanced cirrhosis the increase in the control group (p < 0.001) and the difference between the increase in the two groups (p = 0.001) became more significant. Prothrombin time was also significantly better in the treatment group (p = 0.003). Postoperative complications such as prolonged liver failure, bleeding disorders and infections were seen more often in the control group. In our study MDA-TBARS was increased after liver ischemia, but in patients with advanced cirrhosis the effect was smaller or even absent. This increase and possible clinical consequences of reperfusion injury could be reduced by intraoperative administration of an antioxidant infusion.