Background and Aims The treatment strategies for locally advanced pancreatic cancer (LAPC) are continuously evolving, and with advancements in vascular reconstruction and autologous organ transplantation techniques, the radical resection rate for LAPC with vascular invasion has greatly improved. This study was performed to evaluate the feasibility and safety of extended radical resection of pancreatic cancer with small bowel autotransplantation.Methods The clinical data of two LAPC patients with involvement of the mesenteric root who were treated at the Rocket Force Characteristic Medical Center from May 2022 to May 2023 were retrospectively analyzed. Both patients were female, aged 66 and 58 years, and preoperative imaging indicated malignant tumors within the pancreatic uncinate process, with tumor invasion and encasement of the superior mesenteric artery (SMA) and jejunal artery branches. Both patients had a generally stable preoperative condition but had not undergone chemotherapy due to signs of duodenal obstruction. Preoperative assessments of heart, lung, liver, and kidney function showed that both patients were able to tolerate the surgery. Then, the extended radical resection of pancreatic cancer with small intestinal autotransplantation was performed. The key to the surgery was the simultaneous removal of the small intestine along with the tumor specimen, then rapidly remove the specimen, followed by sequential reconstruction of the SMA/mesenteric vein (SMV) with "artery first, then vein" approach.Results Both patients underwent successful surgeries. In case 1, reconstruction was performed using the inverted splenic artery and the SMA, and the SMV was anastomosed distally to the portal vein (PV). The warm ischemia time of the small intestine was 24 min, and postoperative pathology diagnosed it as poorly differentiated adenocarcinoma of the pancreas. In case 2, end-to-end anastomosis was used for SMA reconstruction, with distal anastomosis of SMV and PV. The warm ischemia time of the small intestine was 18 min, and postoperative pathology diagnosed it as pancreatobiliary-type ampullary carcinoma. Both patients had good postoperative recoveries, with no arterial or venous thrombosis. Their postoperative hospital stays were 25 d and 21 d, respectively. As of August 1, 2023, both patients had been followed up in the outpatient clinic for 12 and 2 months, respectively. During the follow-up period, their general conditions remained good, with no evidence of recurrence or metastasis, except for unstable blood sugar control in case 2.Conclusion Based on the retrospective analysis of these two cases, small bowel autotransplantation for LAPC patients with mesenteric root invasion can be safely and successfully performed. This approach offers a treatment option to relief pain and increase the chances of survival for such patients.