Background: Leakage at the pancreaticoenteric anastomosis remains a common and serious complication after pancreaticoduodenectomy. Over the past decade, various measures directed towards prevention of pancreatic leakage have been studied. This article reviews the available data on the efficacy of these measures. Data sources: The Medline database from 1990 to 2000 was searched for studies on the prevention of pancreatic anastomotic leakage, and the bibliographies of the articles were reviewed for additional references. Results: A meta-analysis of the results of prophylactic octreotide in preventing pancreatic fistula after pancreaticoduodenectomy from data available in three randomized controlled studies yielded an odds ratio of 1.08 (95% confidence interval 0.64 to 1.84). Pending further trials to clarify its role, the routine use of octreotide in pancreaticoduodenectomy cannot be recommended. Retrospective or nonrandomized prospective studies suggested that technical modifications such as duct-to-mucosa anastomosis, pancreaticogastrostomy and external pancreatic duct stenting may reduce the leakage rate, but there is a paucity of randomized trials. A randomized trial comparing pancreaticogastrostomy and pancreaticojejunostomy did not reveal a significant difference in the leakage rate. Conclusions: Further randomized controlled studies are required to determine the optimum technique of pancreaticoenteric anastomosis after pancreaticoduodenectomy.