AIM: The purpose of this study is to find a better operative technique by comparing interrupted stitches with continuous stitches for the outer layer of the pancreaticojejunostomy, i.e. the stitches between the stump parenchyma of the pancreas and the jejunal seromuscular layer, and other risk factors for the incidence of pancreatic leakage. METHODS: During the period January 1997 to October 2004, 133 patients have undergone the end-to-side and duct-to-mucosa pancreaticojejunostomy reconstruction after pancreaticoduodenectomy with interrupted suture for outer layer of the pancreaticojejunostomy and 170 patients with a continuous suture at our institution by one surgeon. RESULTS: There were no significant differences between the two groups in the diagnosis, texture of the pancreas, use of octreotide and pathologic stage. Pancreatic fistula occurred in 14 patients (11%) among the interrupted suture cases and in 10 (6%) among the continuous suture cases (P = 0.102). Major pancreatic leakage developed in three interrupted suture patients (2%) and zero continuous suture patients (P = 0.026). In multivariate analysis, soft pancreatic consistency (odds ratio, 5.5; 95% confidence interval 2.3-13.1) and common bile duct cancer (odds ratio, 3.7; 95%CI 1.6-8.5) were predictive of pancreatic leakage. CONCLUSION: Pancreatic texture and pathology are the most important factors in determining the fate of pancreaticojejunal anastomosis and our continuous suture method was performed with significantly decreased occurrence of major pancreatic fistula. In conclusion, the continuous suture method is more feasible and safer in performing duct-to-mucosa pancreaticojejunostomy.