Preoperative irradiation improves both the resectability and curability of carcinoma of the pancreas head area and should improve patient survival. We retrospectively investigated the value of preoperative irradiation in preventing pancreatic fistula formation. Of 76 consecutive patients who underwent pancreaticojejunostomy by mucosa-to-mucosa anastomosis with a stent catheter after pancreatoduodenectomy, 22 had received preoperative irradiation. The irradiation field included the anastomotic site. In two patients, accidental dislocation of the stent catheter was the apparent cause of fistula formation, but the other 21 patients in the irradiated group developed no fistula. In contrast, nine (17%) of 53 patients in the nonirradiated group developed fistulas. In the irradiated group, preoperative selenomethionine Se 75 scintigraphy revealed a cold area corresponding to the pancreas body, which was included in the irradiation field. Thus, a putative decrease in exocrine function at the pancreatic anastomotic site could explain why fistula formation was prevented by preoperative irradiation.