AIM: To evaluate whether the ABO blood group is related to pancreatic cancer risk in the general population of the United States.METHODS: Using the University of Pittsburgh’s clinical pancreatic cancer registry, the blood donor database from our local blood bank (Central Blood Bank), and the blood product recipient database from the regional transfusion service (Centralized Transfusion Service) in Pittsburgh, Pennsylvania, we identified 274 pancreatic cancer patients with previously determined serological ABO blood group information. The ABO blood group frequency was compared between these patients and 708 842 individual, community-based blood donors who had made donations to Pittsburgh’s Central Blood Bank between 1979 and 2009.RESULTS: The frequency of blood group A was statistically significantly higher amongst pancreatic cancer patients compared to its frequency amongst the regional blood donors [47.63% vs 39.10%, odds ratio (OR) = 1.43, P = 0.004]. Conversely, the frequency of blood group O was significantly lower amongst pancreatic cancer patients relative to the community blood donors (32.12% vs 43.99%, OR = 0.60, P = 0.00007). There were limited blood group B (n = 38) and AB (n = 17) pancreatic cancer patients; the overall P trend value comparing patient to donor blood groups was 0.001.CONCLUSION: The ABO blood group is associated with pancreatic cancer risk. Future studies should examine the mechanism linking pancreatic cancer risk to ABO blood group.