OBJECTIVES: To prevent bacterial endocarditis (BE), the American Heart Association recommends antibiotics prior to urinary catheterization (UC) in the presence of known urinary tract infection (UTI). In young children who undergo evaluation for fever, the presence of UTI is unknown prior to UC. It is the objective of this study to determine the cost-effectiveness of BE prophylaxis prior to UC in febrile children aged 0-24 months with moderate-risk cardiac lesions who present to the emergency department. METHODS: Taking a societal perspective, we determined the cost-effectiveness of BE prophylaxis in terms of 1) quality-adjusted life years (QALYs) and 2) bacterial endocarditis incidence. Probabilities were derived from the medical literature. Costs were derived from national sources in US dollars for the reference year 2000, using a discount rate of 3 percent. Sensitivity analysis was conducted by varying the individual costs and probabilities. RESULTS: When antibiotic-associated deaths are excluded, BE prophylaxis is more effective and more costly than no prophylaxis. Prophylaxis prevents seven cases of BE per 1 million children treated, with an incremental effectiveness of 0.00005 QALYs. The incremental cost-effectiveness ratio of amoxicillin is $10 million per QALY gained and $72 million per case prevented. For vancomycin, it is $13 million per QALY gained and $95 million per case prevented. When antibiotic-associated deaths are included, the no prophylaxis strategy is more effective and less costly than the prophylaxis strategy. The results are otherwise robust to sensitivity analysis. CONCLUSIONS: In the emergency department, BE prophylaxis prior to UC in febrile children aged 0-24 months with moderate-risk cardiac lesions is not cost-effective. The results of this analysis do not support the use of BE prophylaxis in these children.