External drainage of pancreatic juice using a pancreatic duct stent following pancreatoduodenectomy is widely performed. We hypothesized that the replacement of externally drained pancreatic juice would help to prevent postoperative complications, including pancreatic fistulas. Sixty-four patients who underwent pancreatoduodenectomy between 2006 and 2008 were randomly assigned to either a pancreatic juice non-replacement (NR) or replacement (R) group. Eighteen patients were excluded from the analysis because they had unresectable tumors (n = 4), low pancreatic juice output (<100 ml) (n = 11) or for other reasons (n = 3). A total of 46 patients (NR = 24, R = 22) were included in the final analysis. The volume and amylase levels of externally drained pancreatic juice were analyzed on postoperative days 7 and 14. The incidence of postoperative complications, including pancreatic fistulas and delayed gastric emptying, was also assessed. The total amylase secretion from the pancreatic tube on postoperative day 7 was significantly higher in the NR group compared with the R group (P = 0.044). The incidence of pancreatic fistulas (>Grade B) was also significantly higher in the NR group (33.3 vs. 9.1 %, P = 0.046). In cases for whom external pancreatic juice drainage from a stent is applied following pancreaticojejunostomy, enteral replacement of externally drained pancreatic juice may reduce the incidence of postoperative pancreatic fistula formation.