Despite considerable data focused on the morbidity of pancreaticoduodenectomy (PD), the financial impact of complications has been infrequently analyzed. This study evaluates the impact of the most common complications associated with PD on the cost of care. Additionally, we identified cost centers that were significantly affected by complications. A retrospective analysis of a prospective database in a network of community-based teaching hospitals was performed. All patients (n = 145) who underwent PD were included for years 2005 to 2009. Of these, 144 had complete in-hospital cost data. Complications were assessed and classified into major and minor categories according to Dindo et al. Forty-nine cost centers were analyzed for their association with the cost of complications. Univariate and multivariate linear regression analyses were performed. Significance was reported for P < .05. The median cost for PD was $30,937. Patients with major complications had significantly higher median cost compared with those without ($56,224 vs $29,038; P < .001). Independent predictors of increased cost included reoperation; sepsis; pancreatic fistula; bile leak; delayed gastric emptying; and pulmonary, renal, and thromboembolic complications. Cost center analysis showed significant added charges for patients with major complications for blood bank ($1,018), clinical laboratory ($3,731), a computed tomography scan ($4,742), diagnostic imaging ($697), intensive care unit ($4,986), pharmacy ($33,850) and respiratory therapy ($1,090) (P < .05, all). This study identified the major complications of PD, which are significantly associated with a higher cost. Substantial cost center increases were associated with major complications, particularly in pharmacy ($33,850). Measures aimed at limiting complications through centralization of care or care pathways may reduce the overall cost of care for patients after pancreatic resection.