To determine the efficacy of ranitidine in preventing clinically acute overt gastroduodenal (GD) complications (bleeding and/or perforation) after neurosurgery, 101 patients with nontraumatic cerebral disease considered at high risk of developing postoperative GD complications were randomized in a standard double-blind manner to receive either ranitidine (50 mg every 6 hours) or placebo medication preoperatively. Postoperative serial GD endoscopy was used to document the occurrence of complications: an overt symptomatic complication was defined as bleeding requiring blood transfusion and/or surgery. Fifty-two patients received ranitidine and 49 received a placebo preoperatively; 30 developed overt GD bleeding; nine of these received ranitidine and 21 received a placebo. Ranitidine significantly reduced the incidence of bleeding (p < 0.05). Multivariate logistic regression analysis revealed three factors of independent significance in predicting overt GD bleeding: use of a placebo drug, a gastric pH of less than 4, and a high daily volume of gastric output. The authors conclude that ranitidine is useful in preventing postoperative GD complications in high-risk neurosurgical patients.