Purpose: Pancreaticoduodenectomy (PD) is the most frequently performed resectional procedure in chronic pancreatitis. Only a few studies have evaluated quality of life (QOL) after PD for chronic pancreatitis. This retrospective study examined long-term quality of life and relief of symptoms in a homogenous consecutive cohort of 67 patients undergoing PD for chronic pancreatitis. Methods: A standard QOL questionnaire was sent to 168 patients after PD who had undergone PD for chronic pancreatitis at the University Hospital Dresden between 1994 and 2008. QOL and long-term sequelae were evaluated by the EORTC quality of life questionnaire supplemented with complementary questions. Results were compared to general population data based on large random samples. Results: Median follow-up was 69.1 months. Complete response was obtained from 67 (48.5%) patients. Long-term survival of our patients was lower than expected rates based on the Federal Republic of Germany life table analysis (p < 0.001). There was an improved pain control and an increase in weight gain. Overall, QOL scores were slightly inferior to those of the control group. A common problem after PD was onset of diabetes mellitus; however, exocrine function of the pancreas was stable. Conclusions: This is the largest single-institution experience assessing QOL after PD for chronic pancreatitis. Most patients have QOL scores comparable to those of the control patients and can function independently in daily activities.