The role of octreotide in preventing pancreatic fistula following pancreaticoduodenectomy (PD) remains controversial. The purpose of our study was to report our experience with octreotide in 266 patients undergoing PD from 1995 to 2002. There were 150 males and 116 females. Patients were divided into two groups. Group 1 did not receive octreotide (N = 61). Group 2 received octreotide (N = 205). The average patient age was 66.2 years in the control group and 63.6 years in the octreotide group. One hundred fifty patients were male and 116 were female. Thirty-day mortality for both groups was 1.9 per cent. The incidence of pancreatic fistula was 12 per cent. Fistula occurrence in the octreotide group was 13 per cent and in the no-octreotide group 8 per cent (P = 0.34). Common complications in the no-octreotide group were pancreatic leak (10%), pancreatic fistula (8%), and delayed gastric emptying (8%). Common complications in the octreotide group were pancreatic leak (18%), pancreatic fistula (13%), intra-abdominal abscess (7%), and arrhythmia or myocardial infarction (7%). The only statistically different variable was the incidence of arrhythmia or myocardial infarction (P = 0.026). Octreotide did not reduce pancreatic fistula, other complications, or mortality. Octreotide may contribute cardiac morbidity. Octreotide cannot be recommended to prevent mortality or postoperative complications after PD.