Controlled reperfusion of ischemic limbs has been found to be protective in limiting ischemia-reperfusion injury. We aimed to analyze local hemodynamic effects of prostaglandin E1 (PGE1) administrated during controlled reperfusion in an in vivo setting. Twenty-four pigs underwent exposure of the infrarenal aorta and iliac vessels. Pigs were observed for 7.5 h without limb ischemia (group I). In the others, limb ischemia was produced by clamping the aorta for 6 h. Reperfusion was conducted in uncontrolled (group II), controlled (group III), and controlled fashion with addition of PGE1 (group IV) for the initial 30 min. We evaluated regional blood flow in the left common iliac artery, cardiac output, systemic vascular resistance, oxygen and glucose consumption, muscle adenosine triphosphate (ATP), and potassium levels in iliac vein. Benefits after reperfusion were observed in group IV compared with group III regarding regional blood flow at 60 min (P < 0.01) and 90 min (P < 0.01), glucose consumption at 30 min, (P < 0.05) and potassium regulation at 30 (P < 0.05) and 90 min (P < 0.05). The addition of PGE1 to controlled reperfusion further reduces local hemodynamic effects of ischemia-reperfusion injury compared with standard controlled and uncontrolled reperfusion in an animal model.