AbstractAlthough infrequent, acute upper gastrointestinal bleeding is potentially life‐threatening for critically ill patients. Gastric erosions can be detected endoscopically in almost all seriously ill patients. Although gastric acid plays a key role in the pathogenesis of acute gastric erosions, mucosal integrity is very much dependent on mucosal permeability, gastric blood flow, the secretory state of the mucosa, and acid‐base balance. Various agents that affect any of these physiological processes such as vitamin A, carbenoxolone, gastrin, vasoactive agents, sodium bicarbonate, and anticholinergic drugs have been used experimentally or clinically in the prevention of stress ulcerations. However, no controlled clinical trials are available. The effectiveness of antacids in the prevention of acute stress ulceration in critically ill patients has been documented in controlled, prospective trials. The effectiveness of the histamine H2‐receptor antagonist cimetidine remains controversial; it is less effective in critically ill patients of the type usually encountered in a respiratory‐surgical intensive care unit but it may be effective in selected groups of patients with head and thermal injury. Prostaglandins have been evaluated increasingly for their cytoprotective effects on the gastric mucosa. Clinical trials are needed to evaluate their effectiveness in the prevention of stress ulcers.