BACKGROUND: Although antibiotic prophylaxis for infective endocarditis (IE) has been recommended for persons with predisposing cardiac conditions (PCCs) for many years, its efficacy, which has not been demonstrated, has been recently challenged. To assess its usefulness, we estimated the risk of developing IE after undergoing a dental procedure for which subjects would be eligible for prophylaxis, both in subjects having (protected procedure) or not having (unprotected procedure) received antibiotic prophylaxis. METHODS: The number of French persons with PCCs, the annual number of dental procedures in which subjects would be eligible for antibiotic prophylaxis, and the number of procedures that were unprotected were estimated on the basis of a survey performed on a sample of 2805 subjects aged 25-84 years. The annual number of IE cases possibly due to an unprotected procedure was estimated on the basis of a 1-year epidemiological study of IE conducted in an area inhabited by 16 million people. RESULTS: After standardization, extrapolation of results to the age-equivalent general population (39 millions subjects) indicated the following: first, 3.3% (95% confidence interval [CI], 2.6%-4%) of the subjects had PCC, 2.7 million (95% CI, 2.3-3.2 million) of whom had undergone at least 1 at-risk dental procedures within the survey year, and the procedures were unprotected in 62% of cases; second, 37 (95% CI, 18-68; 2.7%) of the 1370 annual IE cases in France were possibly related to unprotected procedures. Thus, the risks of developing IE were estimated to be 1 in 46,000 for unprotected procedures (1 in 10,700 and 1 in 54,300 for subjects with prosthetic and native valve PCC, respectively) and 1 in 150,000 for protected procedures. CONCLUSIONS: A huge number of prophylaxis doses would be necessary to prevent a very low number of IE cases.