PurposeStatin treatment has been shown in certain population studies and meta-analyses to improve survival of patients with pancreatic ductal adenocarcinoma (PDAC). This study assessed if patients with statin treatment had better overall survival (OS) and disease-free survival (DFS) after upfront pancreatoduodenectomy for PDAC.MethodsConsecutive PDAC patients were retrospectively collected from three centers in Europe and USA (study period: 2000–2017). Adult patients who underwent upfront pancreatoduodenectomy and survived the first 90 postoperative days were included. Patients with metastasis at diagnosis or with macroscopic incomplete resection were excluded. Patients were considered under statin if started at least one month before pancreatoduodenectomy. Survival rates were calculated using Kaplan–Meier method and compared with log-rank test.ResultsA total of 496 patients were included. Median age was 67 years (IQR 59–75), 48% (n = 236) were women, and 141 patients (28%) received statin treatment already preoperatively. Patients with and without statin treatment were comparable in terms of demographics and pre-/intraoperative characteristics, except for age and pre-existing diabetes. Median OS and DFS were similar in patients with and without statin treatment (OS: 29, 95% CI 22–36 vs. 27 months, 95% CI 22–32, p = 0.370, DFS: 18, 95% CI 14–22 vs. 16 months, 95% CI 14–18, p = 0.430). On multivariable Cox regression, lymph node involvement (HR 1.9, 95% CI 1.6–2.2, p < 0.001), tumor differentiation (HR 1.3, 95% CI 1.1–1.6, p = 0.003), and postoperative chemotherapy (HR 0.5, 95% CI 0.4–0.7, p < 0.001) were predictors of OS, whereas statin treatment was not a prognostic factor (HR 0.9, 95% CI 0.7–1.2, p = 0.376).ConclusionIn this international cohort of PDAC patients, statin treatment did not influence survival after upfront pancreatoduodenectomy. Nodal involvement, tumor differentiation, and postoperative chemotherapy were independent predictors of OS.