Total pancreatectomy is recommended for intraductal papillary mucinous tumors with widespread involvement of the entire pancreas. Organ-preserving and minimally invasive surgery should be applied in benign and borderline pancreatic lesions. Pylorus- and spleen-preserving total pancreatoduodenectomy (PpSpTPD) with segmental resection of both splenic vessels was attempted for five patients. The technique was based on the concepts of two surgical procedures: pylorus-preserving pancreatoduodenectomy and distal pancreatectomy with segmental resection of splenic vessels ("extended" Warshaw's procedure). Three patients underwent laparoscopic-assisted PpSpTPD and two underwent open surgery. No mortality was noted. Short-term follow-up (median, 28 months) suggested that all patients tolerated the insulin therapy and showed relatively good nutritional status. Only minimal to moderate perigastric fundal varices were noted without gastrointestinal bleeding. PpSpTPD with segmental resection of both splenic vessels is feasible and safe. Even a minimally invasive approach can be indicated in selected patients.