Patients who have undergone pancreaticoduodenectomy (PD) may experience a long-term decrease in quality of life because of postoperative pancreatic dysfunction (such as digestive and absorption disorders) and fatty liver as a result of combined resection of the duodenum, gallbladder, and bile duct. The present study investigated the usefulness of pancrelipase for the prevention of pancreatic dysfunction after PD.The data from 73 patients who underwent PD in a single institution were analyzed. Patients who underwent PD during 2007-2011 were administered the low-titer pancreatic enzyme preparations berizym® and pancreatin® (first period group), while patients who underwent PD during 2012-2017 were administered the high-titer pancreatic enzyme preparation pancrelipase (second period group). The following measures of the nutrition status were examined before and after PD: serum albumin concentration, total lymphocyte count, serum total cholesterol concentration, body mass index, controlling nutrition status (CONUT) index, Onodera's prognostic nutrition index (PNI), and liver computed tomography values.The second period group had significantly higher serum albumin concentrations at 3 and 6 months postoperatively, serum total cholesterol concentrations at 1 month postoperatively, and Onodera's PNI values at 3 and 6 months postoperatively than the first period group. The CONUT index values at 6 months after PD were significantly lower in the second period group than in the first period group.Pancrelipase is useful in improving the nutrition status and preventing fatty liver after PD.