Introduction: For patients who suffer from severe chronic pancreatitis, total or near total pancreatic resection can alleviate pain. Unfortunately, this inevitably results in diabetes that is often brittle. Islet auto-transplantation following pancreatectomy offers a means to preserve endocrine function and circumvent the short and long-term complications of diabetes. Methods: During the period of 2000-2002 we performed 16 total or near-total pancreatectomies with islet-cell auto-transplantation. Postoperative complications, metabolic studies, insulin usage, pain scores, and quality of life were recorded at routine clinic follow-up. Islet cells were harvested through the use of continuous enzymatic perfusion and digestion. Results: Sixteen patients (9 females, 7 males), with a median age of 38 (range, 27-53) underwent total (n=12) or near total (n=4) pancreatectomies with autologous islet-cell transplantation. Of these patients 6 underwent a total pancreatectomy as the initial procedure. The average number of islet-equivalents harvested was 235.315 (range, 20.850-524.417). Operative data revealed a mean estimated blood loss of 597 mL, operative time of 9 hrs and a length of stay of 15 days. Ten patients (63%) had post-operative complications. These included delayed gastric emptying (n=4), pneumonia (n=1), wound infection (n=1), hyperglycemia (n=1), hematoma (n=1), and pulmonary embolism (n=1). There were no deaths in this series. 5 patients underwent peri-operative metabolic testing (arginine stimulation test, oral glucose tolerance test). All patients demonstrated c-peptide and insulin production indicating graft function. With a median follow-up of 16.5 months (range, 1 to 33 months), 69 % of patients are either insulin free (n=7) or require only occasional sliding scale insulin (n=4). All patients had preoperative pain; 100% (N=13/13) had a significant reduction in chronic abdominal pain and an improvement in quality of life as assessed by a SF 36 questionnaire. All patients had a clear reduction in narcotic usage post-operatively. Conclusion: Total or near total pancreatectomy with autologous islet cell transplantation is associated with reduction of abdominal pain and improvement in quality of life. Short-term follow-up demonstrates islet-cell auto-transplantation can prevent the development of surgically induced diabetes and may represent a viable treatment algorithm for severe chronic pancreatitis refractory to medical therapy.