OBJECTIVE Prostaglandin E1 (PGE1) has been used to improve hepatic blood flow and to reduce ischemia reperfusion injuries of allografts in liver transplantation. However, PGE1 undergoes extensive metabolic clearance in the pulmonary and splanchnic circulation during intravenous administration. We analyzed the effect of intraportally administered PGE1. METHODS Sixty living-donor liver transplant recipients received continuous infusions of PGE1 for 10 days immediately after the reperfusion of the allografts. Of them, 40 recipients received PGE1 intravenously (IV group) via the internal jugular vein, and 20 recipients received PGE1 intraportally (IP group) through a catheter in the inferior mesenteric vein. Data were collected for 3 weeks postoperatively. RESULTS The IP group exhibited lower initial aspartate aminotransferase and alanine aminotransferase levels compared with the IV group. However, no apparent differences were recognized in the serum albumin, total bilirubin, alkaline phosphatase, r-glutamyl transpeptidase, or prothrombin time levels between the 2 groups. Chylorous ascites were observed more frequently in the IP group. There was no difference in portal venous flow measured by Doppler sonogram between the 2 groups during the first postoperative week. CONCLUSIONS This study demonstrated that intraportal administration of PGE1 had a better cytoprotective effect against hepatocellular damage than intravenous administration, although it did not have additional benefits for perihepatic hemodynamics.