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The objective of this study was to evaluate the economic outcomes of drug options for stress ulcer prophylaxis in critically ill and/or intensive care unit patients. Decision analytic modelling was used to compare the costs of stress ulcer prophylaxis and possible clinical outcomes [acute upper gastrointestinal bleeding (AUGB) and nosocomial pneumonia]. The regimens evaluated were: antacids, histamine H2 receptor antagonists (H2RAs), sucralfate and no prophylaxis. The results of published studies were pooled to determine the expected probability of AUGB and nosocomial pneumonia following stress ulcer prophylaxis with each of the agents under study. The costs of stress ulcer prophylaxis, treatment of AUGB and treatment of nosocomial pneumonia were identified from various sources. Sucralfate was the least costly agent for stress ulcer prophylaxis. The average net costs per patient for sucralfate, antacids, no prophylaxis and H2RAs were $US1457, $US1737, $US2268, and $US2638 to $US2712, respectively (1994 dollars). No prophylaxis was found to be less costly than giving H2RAs. Sucralfate and antacids, which induced net savings of $US7373 and $US4321 per case of AUGB averted, respectively, were more cost effective than H2RAs. Sensitivity and threshold analyses revealed that the results were constant over a wide range of cost and probability values. Break-even analysis suggested that sucralfate was the optimal agent for stress ulcer prophylaxis unless the acquisition cost of a prophylactic course of sucralfate was > $US304.05 per patient. At that point, antacids become the optimal agent. Based on this analysis, sucralfate may be the most cost-effective agent for stress ulcer prophylaxis in critically ill or intensive care patients.