In a randomized open trial, a regimen consisting of sucralfate administered every six hours was shown to be as effective as a regimen consisting of an antacid given hourly in the prevention of upper gastrointestinal bleeding in 155 patients who were critically ill. Two of 75 (2.6 percent) patients receiving antacid and three of 80 patients (3.8 percent) receiving sucralfate showed evidence of bleeding. In no case was bleeding severe enough to necessitate blood transfusions or surgery. The cost-effectiveness, ease of administration, reduced nursing hours, greater compliance, and fewer side effects make sucralfate a useful substitute for antacid in preventing upper gastrointestinal bleeding in patients who are critically ill.