Purpose/Introduction: The failure to rescue (FTR) rate, defined as the mortality rate following major postoperative complication, is an important marker of the quality of surgical care. This paper examines the multifactorial contributors to FTR following pancreaticoduodenectomy, with an emphasis on identifying perioperative and institutional factors that influence patient outcomes. Methodology: A systematic review was performed in accordance with the PRISMA guidelines. A search was conducted of the Pubmed, Embase, Medline and Cochrane Library databases. Two authors independently reviewed the articles and extracted data for analysis. Results: A total of 10 studies were included for review, with a total of 60158 pancreaticoduodenectomy cases. The FTR rate ranged from 6.9% to 33%. Multiple studies identified advanced age, obesity, pre-existing renal disease and elevated American Society of Anaesthesiologist (ASA) scores to be associated with higher rates of FTR. Patients undergoing re-laparotomy had higher failure to rescue rates but there were mixed results for factors leading to this such as post-operative pancreatic fistulas. Disease-specific features, including pancreatic texture and duct size, were not associated with FTR across studies. Conclusion: FTR is driven less by the occurrence of certain technical or disease-related factors and more by patient vulnerability and the interventions once complications arise.