Background: Pancreaticoduodenectomy (PD) is performed for pancreatic ductal adenocarcinoma (PDA) located at the pancreas head/body. Non-chylous massive discharge after PD is frequently encountered and can cause a vicious cycle of complications associated with severe dehydration and protein loss. Methods: From August 2008 to June 2015, 102 patients who underwent PD for PDA were retrospectively reviewed. High non-chylous discharge was defined as postoperative daily serous discharge exceeding 10 mL/kg. Predictive factors for high non-chylous discharge were assessed using multivariable analysis. Results: Fifty-one patients (50%) developed high non-chylous discharge. Body mass index (BMI) and hemoglobin, total protein, and cholinesterase levels were significantly lower in the high-discharge group compared to the corresponding levels in the low-discharge group. The incidence of postoperative pancreatic fistula and delayed gastric emptying was significantly lower and higher in the high-discharge group than in the low-discharge group, respectively. Multivariable analysis revealed that BMI <22.0 kg/m2, hemoglobin <12.0 g/dL and intraoperative blood loss ≥800 mL were independent predictive factors for high non-chylous discharge. Conclusions: Preoperative low levels of BMI and hemoglobin and intraoperative high blood loss were independent predictive factors for high non-chylous discharge. Improvement of preoperative general and nutritional condition may reduce the incidence of high non-chylous discharge.