OBJECTIVES:Proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) present varying pharmacological efficacy in preventing stress ulcer bleeding (SUB) in intensive care units. The literature also reports disparate rates of ventilator-assisted pneumonia (VAP) as side effects of these treatments. We compared the cost-effectiveness of these two prophylactic pharmacological options. METHODS:We constructed a decision tree with a 60-day time horizon for patients at high risk for developing SUB, receiving either PPIs or H2RAs. For each treatment strategy, patients could be in one of three states of health: SUB, VAP, or no complication. Contemporary, clinically relevant probabilities were obtained from a broad literature search. Costs were estimated by using a representative US countrywide database. A third-party payer perspective was adopted. Cost-effectiveness and univariate and multivariate sensitivity analyses were performed. RESULTS:Probabilities of SUB and VAP were 1.3% and 10.3% for PPIs versus 6.6% and 10.3% for H2RAs, respectively. Lengths of stay and per diem costs were 24 days and US $2764 for SUB, 42 days and US $3310 for VAP, and 14 days and US $2993 for patients without complications. Average costs per no complication were US $58,700 for PPIs and US $63,920 for H2RAs. The H2RA strategy was dominated by PPIs. Sensitivity analysis showed that these findings were sensitive to VAP rates but PPIs remain cost-effective. The acceptability curve shows the stability of the probabilistic results according to varying willingness-to-pay values. CONCLUSION:PPI prophylaxis is the most efficient prophylactic strategy in patients at high risk of developing SUB when compared with using H2RAs.