In order to reduce risk for postoperative acute liver failure, prostaglandin E1 (PGE1) was administered either from the hepatic artery (HA) or the superior mesenteric artery (SMA) in four high-risk cases undergoing major hepatic resection. Two cases were subjected to HA PGE1 infusion for 3 or 4 days after surgery at a rate of 0.01 microg/kg/min. Both patients had hepatocellular carcinoma (HCC) associated with chronic hepatitis, and ICG R15 was 17.6% and 14.5%, respectively. Right hemihepatectomy and extended right hemihepatectomy were performed. Serum total bilirubin (T. Bil.) peak value was 2.2 mg/100 ml in Case 1 and 2.1 mg/100 ml in Case 2. In Case 1, decreased bile flow was observed immediately after cessation of PGE1. The other two cases were subjected to SMA PGE1 infusion for 5 or 6 days after surgery at the same rate. In Case 3, right hemihepatectomy was performed for HCC on a cirrhotic liver four weeks after right portal vein embolization, in which preoperative ICG R15 was 19.0%. Peak T. Bil level was 3.7 mg/100 ml with uneventful postoperative course. In Case 4 with a huge cholangioma, right trisegmentectomy was performed. Peak serum T. Bil level was 1.7 mg/100 ml in this uneventful postoperative course. In Case 3 and Case 4, portal blood flow, measured by Doppler ultrasonography, was markedly increased by PGE1 infusion. From these results, intra-arterial PGE1 infusion might be useful in prevention of postoperative liver failure after major hepatic resection.