Major pancreatic resection is still accompanied by considerable morbidity and even mortality. Complications which occur after pancreatic surgery are chiefly associated with exocrine pancreatic secretion, hence, the inhibition of exocrine pancreatic secretion perioperatively is a promising concept in the prevention of complications. The hormone somatostatin and its synthetic analogue octreotide have been shown to profoundly inhibit exocrine pancreatic secretion, particularly the secretion of proteases. In a randomized, placebo-controlled, multicenter double-blind trial we analyzed the potential role of octreotide in the prevention of postoperative complications after major pancreatic surgery. A significant reduction in complications such as fistula, abscess, fluid collection, sepsis, pulmonary insufficiency, and postoperative acute pancreatitis could be demonstrated in patients who received octreotide at 3 x 100 micrograms/day subcutaneously. Octreotide was particularly effective in patients undergoing Whipple resection for cancer.