Background: Failure to rescue is the concept of death after a complication, and it is an important factor driving variation in mortality rates after pancreatic surgery. The purpose of this study was to conduct a retrospective review of a large, multi-institutional data set to describe patient-level risk factors for failure to rescue in greater detail. Methods: From the American College of Surgeons National Surgical Quality Improvement Program participant use file, 14,557 patients who underwent pancreaticoduodenectomy were identified. Of these, 4514 experienced at least one complication and were therefore at risk for failure to rescue. Multivariable logistic regression models to identify factors independently associated with failure to rescue. Results: Age, American Society of Anesthesiologists class, ascites and/or varices, and disseminated malignancy were significant independent risk factors for failure to rescue. Participation of a resident was associated with reduced odds of failure to rescue. Patients who experienced an initial complication and then accumulated additional complications were more common in the failure to rescue group (68.6% versus 31.3%, P < 0.001). Conclusions: Accumulation of complications after pancreaticoduodenectomy is a significant risk factor for failure to rescue. Pancreatic surgery quality improvement programs should continue developing strategies to identify and intervene on post-pancreatectomy complications, especially in high-risk patients. (C) 2016 Elsevier Inc. All rights reserved.