To determine the precise frequency of main pancreatic duct (MPD) dilatation within the remnant pancreas at 1 year after pancreatoduodenectomy (PD) and its clinical implications, a prospective multicenter cohort study was performed in patients without MPD dilatation before PD (registry number: UMIN000029662). Between October 2017 and July 2020, patients with an MPD diameter less than 3 mm who were planned to undergo PD for periampullary lesions at 21 hospitals were enrolled. The primary endpoints were frequency of MPD dilatation at 1 year after PD, and the relationship between MPD dilatation and pancreatic endo- and exocrine function, nutritional status, and fatty liver. Secondary endpoints were risk factors for MPD dilatation at 1 year after PD and time-course change in MPD diameter. Of 200 registered patients, 161 patients were finally analyzed. Pancreatic fistula was the most frequent complication (76; 47.2%). MPD dilatation (MPD > 3 mm) at 1 year after PD was seen in 35 patients (21.7%). Pancreatic exocrine function, assessed by steatorrhea, was significantly impaired in patients with MPD dilatation. However, endocrine function, nutrition status, and fatty liver development were comparable between the 2 groups. In multivariate analysis, the serum total protein level 7.3 g/dL or more was an independent predictor for MPD dilatation at 1 year after PD (odds ratio 3.12, 95% CI 1.31 to 7.15). A mean MPD diameter significantly increased at 6 months after PD and kept plateau thereafter. MPD dilatation at 1 year after PD was seen in 21.7% of patients and significantly associated with exocrine function impairment but not with endocrine function, nutrition status, or development of fatty liver.