INTRODUCTION: Previous studies identified an association between dilated pancreatic and biliary ducts and lower rates of pancreatic leak after pancreaticoduodenectomy, but it remains unclear whether elevated liver function tests are also associated with lower rates of complications. The purpose of this study was to determine if preoperative liver function tests are associated with postoperative complications. MATERIALS AND METHODS: We identified 452 patients who received a pancreaticoduodenectomy from 1990-2007. Clinicopathological data was collected for each patient, and regression analyses were performed to identify predictors of postoperative complications. RESULTS: Of the patients studied, 289 (64%) experienced no postoperative complications. In univariate analysis, patients with a low or normal preoperative aspartate aminotransferase (p = 0.03) or alkaline phosphatase (p = 0.03), had higher rates of complications. Multivariate analysis confirmed an elevated alkaline phosphatase was associated with a lower incidence of complications (OR = 0.56, p = 0.02), while preoperative anemia was found to be a predictor of complications following pancreaticoduodenectomy (OR = 2.01, p = 0.02). CONCLUSION: Anemic patients and those with normal liver function tests were more likely to experience complications after pancreaticoduodenectomy. This may represent extent of disease and tumors not causing biliary or pancreatic dilatation, respectively. Precautions, such as intraoperative ductal stents, should be considered when operating on this group of patients to minimize complications.