Autologous islet cell transplantation after near-total or total pancreatic resection can alleviate pain in patients with severe chronic pancreatitis and preserve endocrine function. From February 2000 to February 2003, a total of 22 patients, whose median age was 38 years, underwent pancreatectomy and autologous islet cell transplantation. Postoperative complications, metabolic studies, insulin usage, pain scores, and quality of life were recorded for all of these patients. The average number of islet cells harvested was 245,457 (range 20,850 to 607,466). Operative data revealed a mean estimated blood loss of 635 ml, an average operative time of 9 hours, and a mean length of hospital stay of 15 days. Sixty-eight percent of the patients had either a minor or major complication. Major complications included acute respiratory distress syndrome (n = 2), intra-abdominal abscess (n = 1), and pulmonary embolism (n = 1). There were no deaths in our series. All patients demonstrated C-peptide and insulin production indicating graft function. Forty-one percent are insulin independent, and 27% required minimal amount of insulin or a sliding scale. All patients had preoperative pain and had been taking opioid analgesics; 82% no longer required analgesics postoperatively. Pancreatectomy with autologous islet cell transplantation can alleviate pain for patients with chronic pancreatitis and preserve endocrine function.