BACKGROUND & AIMS: Although many individuals with pancreatic cancer have diabetes, the association between new-onset diabetes mellitus and the subsequent incidence of pancreatic cancer is unclear. METHODS: We conducted a retrospective cohort study to estimate the incidence of pancreatic cancer subsequent to a new diabetes diagnosis and to evaluate factors associated with a subsequent pancreatic cancer diagnosis. We used the Veterans Health Administration National Patient Care Database to assemble a cohort of 1,421,794 US veterans without prior diabetes or pancreatic cancer diagnoses. We recorded coding for new diabetes diagnoses (> or =2 International Classification of Diseases-9 codes for diabetes within a 12-month period), pancreatic cancer, age, sex, race, and common gastrointestinal symptoms. RESULTS: A total of 36,631 (2.6%) of the 1,421,794 veterans were diagnosed with new-onset diabetes in 1999; 149 subsequently received a diagnosis of pancreatic cancer. Pancreatic cancer incidence in patients with new-onset diabetes (83.8/100,000 person-years) was 2.2-fold higher (95% confidence interval, 1.84-2.56) than in nondiabetics, and was highest during the first 2 years after diabetes diagnosis. One additional pancreatic cancer was diagnosed for every 332 new diabetics over 6 years. A subsequent pancreatic cancer diagnosis (among new-onset diabetics) was associated independently with younger age groups, changes in bowel habits, constipation, epigastric pain, and malnutrition. CONCLUSIONS: New-onset diabetes was associated with a significantly increased rate of pancreatic cancer diagnosis, particularly in the first 2 years after diabetes diagnosis. Factors associated with pancreatic cancer diagnosis included younger age groups and the presence of gastrointestinal symptoms. The absolute incidence of pancreatic cancer was low.