The records of 131 consecutive patients with periampullary carcinoma who underwent pancreaticoduodenectomy within a 12-year period were reviewed to determine the perioperative risk factors of pancreaticojejunal (PJ) anastomotic leak. Twenty-one PJ leaks were identified, for a frequency of 16% (21 of 131); 19% (4 of 21) of these patients eventually died of PJ leak-related complications. A total of 23 items of perioperative data, presumed as risk factors predisposing to PJ leak, were examined. By univariate analysis, advanced age, prolonged duration of untreated jaundice, deep jaundice, decreased creatinine clearance, increased intraoperative blood loss, and shock during operation were statistically significant. However, by multivariate analysis, only duration of jaundice, creatinine clearance, and intraoperative blood loss turned out to be independent risk factors. Noteworthily, jaundiced patients with impaired creatinine clearance not only had a higher incidence of PJ leak, but were also more liable to experience sepsis and intraabdominal bleeding, which uniformly elicited a grave clinical course. Routine preoperative biliary drainage failed to enhance the security of PJ. Completion pancreatectomy continued to carry a poor prognosis, and should be avoided when possible and replaced by early, aggressive radiologic intervention.