BACKGROUND: Pancreatoduodenectomy (PD) represents one of the most technically demanding surgical procedures, characterized by extensive surgical trauma and high perioperative morbidity. Single outcome measures are insufficient to comprehensively assess the surgical quality of PD. Textbook outcome (TO), as an integrated evaluation system incorporating multiple clinical parameters, offers an objective, reliable, and comprehensive assessment of surgical performance. This systematic review and meta-analysis aimed to identify risk factors associated with failure to achieve textbook outcome (non-TO) following pancreatoduodenectomy. MATERIALS AND METHODS: We systematically searched international databases (PubMed, Web of Science, EMBASE, and Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, Weipu Chinese Journals Service Platform, Wanfang Data, and SinoMed) for studies on risk factors of failure to achieve textbook outcome after pancreatoduodenectomy from inception to 31 December 2024. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models. Heterogeneity testing, sensitivity analysis, and publication bias assessment were conducted. RESULTS: Ten studies involving 5238 patients were included in this meta-analysis. Among the 18 factors evaluated, five were significantly associated with failure to achieve textbook outcome after pancreatoduodenectomy: preoperative biliary drainage (OR = 2.09, 95%CI [1.30-3.36], P = 0.002), smaller tumor size (OR = 1.36, 95%CI [1.02-1.81], P = 0.04), soft pancreatic texture (OR = 2.25, 95%CI [1.01-5.02], P = 0.05), small pancreatic duct diameter (OR = 2.30, 95%CI [1.62-3.28], P <
0.00001), and increased intraoperative blood loss (OR = 4.14, 95%CI [1.16-14.83], P = 0.03). The remaining 13 factors showed no significant association with failure to achieve textbook outcome. CONCLUSION: This meta-analysis identified preoperative biliary drainage, tumor morphological characteristics (including size and texture), pancreatic duct diameter, and intraoperative blood loss as key factors affecting the achievement of textbook outcome after pancreatoduodenectomy. These findings may help surgeons identify high-risk patients for failure to achieve textbook outcome, enabling personalized surgical strategies and optimized perioperative management to improve textbook outcome rates.