A significant fraction of patients undergoing pancreaticoduodenectomy (PD) develop a postoperative pancreatic leak. Previous randomized, placebo-controlled trials have evaluated prophylactic octreotide use in patients undergoing pancreatic resection. Trials from Europe have shown some benefits, however these findings were not reproduced in trials from the US. Therefore, prophylactic use of octreotide for this purpose remains in debate. A high risk group for pancreatic fistula can be established after PD and a special care as prophylactic use of octreotide might reduce the incidence of pancreatic fistula and its complications.Objective: This study was conducted to determine whether the administration of prophylactic octreotide decreases the incidence of pancreatic anastomotic leak after PD in a group with high risk to develop pancreatic fistula.Methods: Based on previous reports from our service the occurrence of pancreatic fistula after PD is significantly higher when the amylase level in the abdominal drain fluid on postoperative day 1 is > 1000UI/dL.Between January 2004 and July 2007, 97 patients were recruited into this study on the basis of preoperative indication of PD resection. Patients who had amylase level content > 1000UI/dL in the abdominal drain on postoperative day 1 were randomized to control versus octreotide 100 mcg subcutaneously three times a day for 10 days. The primary postoperative endpoints were pancreatic fistula occurrence, clinical classification of pancreatic fistula, and length of hospital stay.The definition of pancreatic fistula was a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase content greater than 3 times the serum amylase.Results: Thirty five patients submitted to PD with pancreatic-enteric anastomosis had amylase level > 1000UI/dL in the abdominal drain on postoperative day 1 and were randomized to control versus octreotida treatment. The two groups were comparable with respect to demographics aspects. The pancreatic fistula rates were 62.5% in the control group and 72.2% in the octreotide group. The clinical classification of pancreatic fistula were type A - 64%, type B - 27% and type C - 9% in the control group and type A - 54%, type B - 31% and type C - 15% in the octreotide group. The median postoperative length of hospital stay was 11 days in both groups.Conclusions: These data demonstrate that the occurrence of pancreatic fistula, fistula related complications, and hospital stay after pancreaticoduodenectomy are not reduced by prophylactic use of octreotide in a high risk group to develop postoperative pancreatic fistula.