Background: Pancreatectomy or drainage has been advocated for pain due to chronic pancreatitis. Islet cell autotransplantation (IAT) may improve quality of life (QOL); optimal patient selection has not been established. Study Design: Outcomes of 100 patients who underwent pancreatectomy with islet isolation between 2005 and 2012 were assessed by etiology (alcoholic pancreatitis [AP] 30%, and nonalcoholic pancreatitis [NAP] 70%). Insulin requirement, Short Form-36, and McGill Pain Questionnaires were assessed. Data were analyzed using SASv9.2. Results: Of the 100 patients, isolation was unsuccessful in 9 patients due to fibrosis. Alcoholic pancreatitis was associated with 7 of 9 failed isolations (23% vs 3%, p < 0.01), and all of these patients are now diabetic. Ninety-one patients (age 44 years, follow-up 19 months, 23% AP) underwent resection with IAT. Total islet yield (islet cell equivalents [IEQ]) and IEQ/kg body weight were less for patients with AP (81,000 vs 150,000, p < 0.01; 1,260 vs 2,190, respectively, p = 0.01) overall and more specifically, for total pancreatectomy (92,000 vs 188,000, respectively, p = 0.02). Twenty-eight (34%) of all patients who had resections and 15% of those undergoing total pancreatectomy are insulin free. Multivariate analysis identified AP as an independent predictor of insulin units/day (p = 0.01). Complete pre- and postoperative QOL and pain surveys were available on 69 patients. Patients with AP had less QOL improvement (1 of 8 vs 5 of 8 domains, p < 0.01) and "present pain" improvement at 2 years from preoperative levels in those with NAP; no improvement in QOL was seen in those with AP (NAP 2.7 to 1.2, p < 0.01; AP 2.7 to 2.2, p > 0.05). Conclusions: After pancreatic resection with planned IAT, AP resulted in failed isolations, lower yields, higher insulin requirements, poor long-term QOL improvement, and no improvement in pain scores compared with NAP. Further studies should define criteria for resection and IAT for patients with alcoholic chronic pancreatitis. © 2013 by the American College of Surgeons.