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Survival in pancreatic cancer remains poor with curative potential dependent on operative resection. We reviewed national adherence to practice guidelines to evaluate regional variation in the treatment and survival of patients with pancreatic cancer.Retrospective cohort review of adults with pancreatic adenocarcinoma using the National Cancer Data Base from 2006 to 2013. Overall survival was compared by the Kaplan-Meier method and Cox proportional hazards models. Sequential multivariate logistic regression models were generated for odds of: a) diagnosis in stage I/II, b) resection, and c) receipt of multimodality therapy, defined as operative resection plus chemotherapy with or without radiation. Five geographic regions of the United States were used for analyses.A total of 115,952 patients were identified. At least 22% of patients in all stages received no treatment, with only 38.4% and 32.3% of stage I and II patients receiving multimodality therapy. On unadjusted analysis, the Northeast had the greatest survival for all stages of disease, most pronounced for stage I where patients lived 2 to 3 more months (log-rank P < .0001). While adjusted odds of early diagnosis and resection were comparable or greater across regions relative to the Northeast, patients who underwent resection in the Northeast were significantly more likely to receive multimodality therapy. Multivariate Cox modeling for patients receiving multimodality therapy accounted for differences in 3 of 4 remaining regions.Regional variations exist in pancreatic cancer treatment and survival. While providing multimodality cancer-directed therapy can help mitigate these differences, survival with pancreatic cancer needs to be interpreted in the context of overall health, underlying risk factors, and life expectancy.