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Background: Patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic ductal adenocarcinoma (PDAC). We present data on PDAC in one of the most extensive European single-centre cohort studies of patients with CP. Methods: Retrospective analysis of prospectively collected data of patients with CP was performed. Aetiology of CP was determined according to the M-ANNHEIM classification system and only patients with definite CP > 18 years at data analysis were included. The final dataset included 581 patients with definite CP diagnosed between 2003 and 2018. Results: At CP diagnosis, there were 371 (63.9%) males and 210 (36.1%) females (median age 57 years, range 2–86). During 3423 person-years of observation, six pancreatic cancers were diagnosed (0.2% year). The mean time between diagnosis of CP and the occurrence of PDAC was 5.0 years (range 2.7–8.6). None of the cancer patients had a family history of PDAC. Diabetes mellitus (DM) was present in five of six (83.3%) patients with PDAC: in three patients before and in two after CP diagnosis. Clinical/laboratory signs of pancreatic exocrine insufficiency (PEI) were present in five of six (83.3%) patients with PDAC: in two at diagnosis of CP and in three after diagnosis. The mean survival time was 4 months after the diagnosis of PDAC (range 0.5–13). PDAC occurred significantly more often (p < 0.001) in two groups of patients without previous acute pancreatitis (AP): 2 of 20 patients (10%) with low body mass index (BMI) and PEI and in 3 of 10 (30%) patients with high BMI and DM at diagnosis of CP. Conclusions: Patients with CP have a high risk …