Background: Pancreatic fistula (PF) is one of the most common complications following pancreaticoduodenectomy (PD). Objective: This study was designed to evaluate pancreatic duct stenting in patients undergoing PD. Methods: Between March 2004 and October 2005, nine surgeons performed PDs on 224 patients. Patients were randomized to either pancreatic stent (PS) or no stent (NS) placement. Patients who randomized to the PS group had a 6 cm stent placed. All pancreaticojejunal (PJ) anastomoses were hand sewn in two layers. Recorded variables included pancreas texture (soft vs. hard), diameter of the pancreatic duct, diameter of the pancreatic stent, PJ technique (invagination vs. duct-to-mucosa), PJ orientation (end-to-side vs. end-to-end) and the number of drains placed. The primary endpoint was the PF rate, as defined by an International Study Group (Surgery 138; 8, 2005) as drain fluid amylase greater than three times the normal serum level, on or after the third postoperative day. The study conclusions were similar when the definition for PF used in prior studies from our institution was applied (over 50 ml of drain output containing amylase rich fluid, on or after the tenth postoperative day). Secondary endpoints included postoperative length of stay and mortality. Results: There were 220 patients included in the final analysis (four patients were withdrawn from the study because their ducts could not be stented). The PF rate for the total cohort was 22.7% (11.4% when applying the abovementioned institutional definition of PF). There were 113 patients in the NS group and 107 patients in the PS group. Age and gender distribution were statistically similar between the two groups. The two groups were also similar for each of the evaluated endpoints, including PF rate (20% NS vs. 25% PS, p=0.4), postoperative length of stay (median, 7 days NS vs. 8 days PS, p=0.7), and perioperative death (3% NS vs. 2% PS, p=0.7). The results of a multivariate logistic regression analysis are presented in the table. A soft pancreas and a small pancreatic duct were associated with an increased risk for developing a PF, independent of the use of a stent. Conclusion: Inclusion of a pancreatic duct stent in the PJ anastomosis does not reduce the incidence of PF following PD. Two factors independently associated with PF are a soft pancreas and a small pancreatic duct.