PurposePancreatic ductal adenocarcinoma (PDAC) has been shown to have a lower incidence in patients with blood group O. It is currently uncertain if patients with group O have a better prognosis after pancreatectomy. This study assessed the overall survival (OS) and disease-free survival (DFS) of PDAC patients who underwent upfront pancreatoduodenectomy based on ABO blood groups.MethodsA cross-sectional study was performed including patients from two university centers. All consecutive head PDAC patients who underwent upfront pancreatoduodenectomy from 2000 to 2016 were included. OS and DFS were compared between blood groups A, B, AB, and O using Kaplan-Meier curves and log-rank tests.ResultsA total of 438 patients were included (215 women, median age 67). Pre- and intraoperative details were comparable between all subgroups. Median OS did not differ between the four blood groups (A: 23 months, 95% CI 18–28; B: 32, 95% CI 20–44; AB: 37, 95% CI 18–56 and O: 26, 95% CI 20–32, p = 0.192). Median DFS were also similar (A: 19 months, 95% CI 15–23; B: 26, 95% CI 19–33; AB: 35, 95% CI 15–55 and O: 22, 95% CI 15–29, p = 0.441). There was no OS difference between O and non-O groups (median: 26 months, 95% CI 20–33 vs. 25 months, 95% CI 20–30, p = 0.773). On multivariable analysis blood groups were not prognostic of OS. Only lymph node involvement, tumor differentiation, and adjuvant chemotherapy were independent prognostic factors.ConclusionOS and DFS were similar between all four blood groups after pancreatoduodenectomy. Independent predictors of OS were associated with tumor characteristics and adjuvant treatment.