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Background: Due to improved detection of pancreatic lesions, the resection of non-malignant tumors and indeterminate masses has increased. Prior studies have examined outcomes of pancreaticoduodenectomy (PD) performed for malignancy, but few have examined the long-term implications of this operation for non-malignant lesions.Aims: To assess the long-term outcomes, quality of life (QOL), and need for invasive procedures in patients undergoing PD for non-malignant disease.Methods: Patients undergoing PD for non-malignant disease between 2006-2010 were retrospectively identified and contacted to complete a symptom survey. Charts were reviewed for imaging studies, hospital admissions, and invasive procedures. Subjects were surveyed regarding disease specific QOL parameters and complications occurring six months or more post surgery. Information from the phone survey was verified with review of outpatient records.Results: Eighty patients were identified from the surgical database (77 pylorus preserving, 3 classic), out of 413 PDs performed over the same period of time, of whom 33 completed the phone survey. Median age was 67 yrs. Median follow up was 3.1 yrs. Diagnoses were IPMN (67.5%), chronic pancreatitis (20%), SCA (11.3%), and MCN (1.3%). New diabetes developed in 19.2% with 60% of those new diabetics requiring insulin. Of those with pre-operative diabetes, blood sugars were more difficult to control in 42.3%, insulin was initiated in 28.6%. Overall, 18.2% of patients initiated insulin during the follow-up. Chronic abdominal pain occurred in 27.3% of patients, negatively impacting daily function in 6.1% and requiring chronic opiates in 3.0%. Increased bowel frequency was seen in 39.4 % with improvement in only half of those treated with pancreatic enzymes. Bowel frequency adversely affected patients on a daily basis in 9.1%. Overall, 36.3% of patients surveyed developed diabetes or a postoperative symptom that negatively impacted their daily life. The exclusion of patients with chronic pancreatitis did not significantly change this number (33.3%). Ten patients (12.5%) required ERCP for management of pancreatico- or choledocho-jejunal anastomotic strictures, 2 patients required Puestow procedures, and incisional hernias were repaired in 5 patients (6.25%). Three patients (3.8%) died during the follow-up period; none were related to the PD.Conclusions: This study reports the long-term outcome of PD performed for non-malignant diseases. A minority (36.3%) of patients developed post-operative symptoms that negatively impacted their daily function including diabetes, chronic pain, and diarrhea. Post-operative endoscopic and/or surgical interventions were rare. Careful consideration of post-operative quality of life should be considered when planning pancreatic resection for non-malignant lesions.