Although pancreaticoduodenectomy has become a safe and effective procedure for benign and malignant pancreatic diseases in recent years, leakage of pancreaticoenteric anastomosis still remains a major cause of morbidity and even mortality. Various methods have been used to prevent pancreatic fistula with either pharmacologic or technical approaches. Based on meta-analysis of results from European and American trials, prophylactic use of octreotide to inhibit pancreatic secretion cannot be recommended for routine use in pancreaticoduodenectomy. Further randomized trials are required to clarify the role of selective use of octreotide in patients at high risk for pancreatic leakage. Technical improvement by surgeons is probably the most important approach to reduce pancreatic anastomotic leakage rate. Various technical modifications for pancreaticoenteric anastomosis have been suggested; some have been tested in randomized controlled trials, but data from randomized trials are generally scarce. Use of PG instead of PJ anastomosis, internal stenting of PJ anastomosis, pancreatic duct occlusion, and fibrin glue have not been shown to be effective in reducing pancreatic leakage rate after pancreaticoduodenectomy. One randomized trial recently showed significant reduction of pancreatic leakage rate using an external diverting stent after PJ anastomosis, and another randomized trial showed significant reduction in PJ anastomosis leakage using the binding PJ anastomosis technique. Nonetheless, further high-quality randomized controlled trials are needed to evaluate the benefit of these technical modifications in decreasing the pancreatic leakage rate after pancreaticoduodenectomy.