BACKGROUND The mechanism by which diabetes mellitus (DM) impacts the association between ABO blood types and pancreatic cancer is unclear. MATERIAL AND METHODS A retrospective case-control study of 264 patients with pancreatic cancer and 423 age- and sex-matched individuals with nonmalignant diseases was performed to assess whether ABO blood group and DM jointly contribute to pancreatic cancer risk. RESULTS A multivariate analysis with adjustments for risk factors revealed that blood type, chronic pancreatitis, and DM were significantly associated with increased pancreatic cancer risk. The estimated adjusted odds ratios (AORs with 95% confidence intervals [CIs]) were 2.130 (1.409-3.220) for blood type A, 2.383 (1.313-4.325) for blood type AB, 1.518 (1.012-2.276) for DM, and 10.930 (1.202-99.405) for chronic pancreatitis. Blood type A significantly modified the risk for pancreatic cancer in individuals with DM (AOR, 3.506; 95% CI, 1.659-7.409). CONCLUSIONS The risk for pancreatic cancer was associated with ABO blood type, DM, and chronic pancreatitis in a Chinese population. The risk was greatest for individuals with blood type A and DM.