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Variability in blood use after pancreaticoduodenectomy and the associated impact on readmission, mortality, and cost is not well understood at the national level.The University HealthSystem Consortium database was queried for all pancreaticoduodenectomies performed between the years 2011–2013 (n=9,582). Patients were grouped according to transfusion requirements into none (0 units, 64%), low (1–2 units, 15%), medium (3–5 units, 13%), and high (>5 units, 8%). Multivariable analyses were used to determine predictors of increased transfusions, readmission, in-hospital mortality, and cost.Of the patients undergoing pancreaticoduodenectomy, 36% received blood perioperatively. Patients with high transfusion requirements were less often white, more often male, and had a higher severity of illness (all P < .01). High transfusion requirements correlated with higher readmission rates (OR 1.23, P=.03), cost (RR 1.84, P < .01), length of stay (18 vs. 13 vs. 10 vs. 8 days, P < .01), and in-hospital mortality (12.5% vs. 3.1% vs. 0.5% vs. 0.4%, P < .01). Higher-volume surgeons demonstrated lower transfusion requirements (OR 0.61, P < .01).Significant variability exists nationally in transfusion practices for patients undergoing pancreaticoduodenectomy, which may be driven most by severity of illness and surgeon volume. Efforts to reduce such variability could lead to improved outcomes and healthcare cost savings.