BACKGROUND Recent studies have questioned the use of histamine (H2) receptor antagonist in stress ulcer prophylaxis because of an increased incidence of nosocomial pneumonia and subsequent death. METHODS This prospective randomized study compared prophylaxis with cimetidine vs sucralfate. METHODS Medical/surgical intensive care unit in Springfield, Mass. METHODS One hundred fourteen patients were enrolled. METHODS Cimetidine, administered as a primed continuous infusion using a 300-mg bolus followed by 37.5 mg/h, was compared with sucralfate, administered via nasogastric tube, at a dosage of 1 g every 6 hours suspended in 20 mL of sterile water. METHODS End points of the study included nosocomial pneumonia, gastrointestinal hemorrhage, and death. RESULTS Fifty-six patients were randomized to receive cimetidine and their rate of pneumonia was 12.5%; upper gastrointestinal hemorrhage, 3.6%; and mortality, 33.9%. Fifty-eight patients were given sucralfate, and their rate of pneumonia was 13.8%; upper gastrointestinal hemorrhage, 3.4%; and mortality, 37.9%. There were no significant differences between these study end points. In patients who had pneumonia, 80% of isolates were aerobic gram-negative bacilli. CONCLUSIONS These observations suggest that the rate of nosocomial pneumonia is not increased in patients in the intensive care unit who receive prophylaxis with cimetidine to prevent stress ulcer bleeding.