Background: Pancreatic resection can alleviate pain in properly selected patients with severe chronic pancreatitis, but often at the expense of inducing “brittle” diabetes. Islet cell autotransplantation (IAT) has been shown to decrease diabetes-related morbidity. Aim: To evaluate quality of life and severity of pain in patients undergoing pancreatic resection with IAT for chronic pancreatitis. Methods: All patients undergoing pancreatectomy with IAT from April 2005 to December 2008 were evaluated. Data were collected by chart review and query of hospital databases. Quality of life was measured by the Short Form-36 (SF-36) and severity of pain was measured by the McGill Pain Questionnaire-Short Form (MPQ-SF). Surveys were completed preoperatively, at routine 6-month and 1-year follow-up visits, and after distribution by mail. Norm-based scoring was used for the SF-36 so scores were standardized to the general population mean. The MPQ-SF includes a visual analog scale in addition to written questions. Results are reported as median ± interquartile range or as a percentage. Statistical analyses were conducted with SAS version 9.3.1. Results: Forty-two consecutive patients who underwent 43 pancreatic resections with IAT were identified. For the 29 total pancreatectomy and 14 pancreatoduodenectomy cases, islet equivalents infused was 77,227 ± 179,429 and 13,889 ± 50,832 and islet equivalents per gram of pancreas was 2566 ± 3639 and 841 ± 2536 for each procedure, respectively. At median follow-up of 6.1 ± 11 months, cessation of narcotic use was reported by 70% of patients. SF-36 surveys were completed by 30, 17, and 14 patients and the MPQ-SF was completed by 30, 15, and 13 patients preoperatively, at 6-months, and at 1-year, respectively. SF-36 physical component scores were higher at 6-month and 1-year follow-up when compared with preoperative values (p=0.001) and improvement was observed in 5 of 8 scales (p<0.05). At 6-months and 1-year after surgery, 82% and 67% of patients felt that they were “better off than 1 year ago,” respectively (p<0.0001). MPQ-SF scores improved in all domains (p<0.005), including total score (p=0.001) and visual analog scale (p<0.001). No patients have been hospitalized for hypoglycemic complications and there was one unrelated death at 2 years. Conclusions: In appropriately selected patients with chronic pancreatitis, pancreatic resection with IAT is safe, provides effective pain relief, and improves quality of life. Patients with severe chronic pancreatitis should be considered for pancreatic resection with IAT at a center with this capability.