Total pancreatectomy with islet autotransplantation is an emerging surgical technique for management of chronic pancreatitis. By removing the entire root cause of pain, total pancreatectomy allows for a significant reduction, if not outright resolution, of the pain and feeding intolerance associated with chronic pancreatitis, while the islet autotransplant component mitigates the risk of significant brittle diabetes after the pancreatectomy. Preoperative assessment and management of comorbidities, nutritional status, and variations in operative anatomy are critical for limiting peri- and postoperative morbidities. Perioperatively, lines for patient monitoring are placed, including arterial lines for intraoperative monitoring of blood pressure, intravenous catheters for infusions, oro- or nasogastric tubes for decompression, a Foley catheter, and a paravertebral catheter for pain control. Exposure and removal of the pancreas follows a strict procedure so that the blood supply is maintained until the last step to minimize warm ischemia. While the pancreas is processed outside the operating room to isolate the islets, a Roux-en-Y is created. Finally, the isolated islet cells are infused through the stump of the splenic vein or middle colic vein. Although minimally invasive techniques are possible and are associated with shorter hospital stays and less narcotic use, the unpredictable degree of scarring and inflammation due to chronic pancreatitis can increase the difficulty of these procedures.