Background: Aorto-femoral bypass surgery is associated with remote organ injury due to ischemia-reperfusion injury. The aim of this study was to compare general anesthesia supplemented with dexmedetomidine infusion with epidural anesthesia regarding the ability to attenuate ischemia-reperfusion injury during aorto-femoral bypass surgery by measuring malondialdehyde serum level before and after revascularization. Methods: 52 patients scheduled for aorto-femoral bypass surgery were included in the study. Patients were randomized into two groups, group EP anesthetized by epidural anesthesia and group GA anesthetized by general anesthesia supplemented with dexmedetomidine infusion. Malondialdehyde serum level was measured using ELISA kit and optical density method. Hemodynamic variability was recorded at different time points during the study. Intra-operative data (duration of surgery, duration of cross clamping, estimated blood loss, volume of given crystalloids, colloids, packed RBCs, fresh frozen plasma) were all recorded. Post-operative complications (hypertension, tachycardia, hypotension, bradycardia and shivering) were also recorded. Results: Malondialdehyde serum levels were significantly lower in the GA group at 2hrs. and 5 hrs. after revascularization but not after 24hrs. Heart rate was significantly lower in the GA group through most of the operation time. Post-operative hypertension and tachycardia were significantly higher in the GA group were as post-operative shivering was significantly higher in the EP group. Conclusion: Dexmedetomidine supplementation to general anesthesia can attenuate ischemic-reperfusion injury after 2 and 5hrs. of revascularization more than epidural anesthesia can do alone. Hypertension and tachycardia are more common after discontinuation of dexmedetomidine in the post-operative period. Shivering is significantly reduced after dexmedetomidine infusion