Pancreatic fistula remains one of the most common complications of pancreaticoduodenectomy. This study was carried out to identify relevant risk factors for the development of pancreatic fistula and to evaluate whether prophylactic administration of octreotide decreases their incidence. Between March 1985 and December 2001, 129 consecutive patients who underwent elective pancreaticoduodenectomy for pancreatic or ampullary carcinomas were prospectively evaluated. Pancreatic fistula was defined as drainage of at least 10 mL of amylase-rich fluid detected in abdominal drains after the 3rd postoperative day. The overall postoperative complication rate was 36.4% (n=47) and pancreatic fistula was found in 12.4% (n=16) of patients. No differences were found between patients receiving octreotide and the non-octreotide group regarding the incidence of postoperative complications, including pancreatic fistula. Univariate and multivariate analysis of factors predicting the development of pancreatic fistula showed that only soft pancreatic texture (p=0.0002) and ligation of the pancreatic remnant (p=0.029) were significantly associated with fistula formation. The only surgeon-dependent factor which may reduce the incidence of stump-related complications is anastomosis of the pancreatic remnant with the alimentary tract. Carried out single-institution analysis showed octreotide to be ineffective in the prevention of pancreatic fistula following pancreaticoduodenectomy.