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Operation for hepato-pancreato-biliary cancer is among the most invasive open abdominal operations, with a high postoperative morbidity and mortality rate. The purpose of the present study is to investigate whether a preoperative 6-minute walk distance can predict major postoperative complications after operation for hepato-pancreato-biliary diseases.A total of 81 participants who underwent pancreaticoduodenectomy, major hepatectomy with extrahepatic bile duct resection, or hepatopancreatoduodenectomy were included. The 6-minute walk distance was performed within 1 week before operation. Patients were categorized into 2 groups based on surgical complications: Clavien-Dindo grade <3 and Clavien-Dindo grade ≥3. Clinical differences between the 2 groups were analyzed. Multivariate logistic regression analysis was performed to identify risk factors for postoperative complications that were categorized as Clavien-Dindo grade ≥3.The multiple logistic regression model revealed a significant correlation between major postoperative complications and preoperative low 6-minute walk distance, low body mass index, and major blood loss. In patients with 6-minute walk distance <400 m (1,312 feet), the Clavien-Dindo grade was considerably greater than patients with ≥400 m.The 6-minute walk distance is useful in identifying patients with a greater chance of developing major postoperative complications after surgery for hepato-pancreato-biliary cancer.