In 1981, we developed the first antithrombogenic bypass catheter for the portal system. This catheter-bypass procedure relieved the time limitation caused by portal occlusion and facilitated safe and easy resection and reconstruction of the portal vein or hepatic artery. We thereafter explored isolated pancreatoduodenectomy, in which pancreatoduodenectomy is performed under non-touch isolation techniques. It is difficult to perform isolated pancreatoduodenectomy because of the complex arterial anatomy of the peripancreatic head region. In 1992, a mesenteric approach was developed for pancreatoduodenectomy. This approach allows dissection from the non-cancerous side and determination of both cancer-free margins and resectability followed by systematic lymphadenectomy around the superior mesenteric artery. This approach also enables early ligation of the inferior pancreatoduodenal artery and dorsal pancreatic artery branches from the superior mesenteric artery, as well as complete excision of the total mesopancreas (which is thought to be the second portion of the pancreatic head nerve plexus). Through this development of the mesenteric approach and antithrombogenic catheter-bypass procedure, our isolated pancreatoduodenectomy was finally established in 1992. This is the ideal surgery for pancreatic head cancer from both surgical and oncological aspects. We herein introduce the precise surgical techniques.