Approximately 10% of the population claim to be allergic to penicillins, but only approximately 10%-30% of these have IgE-mediated reactions to penicillin skin tests. Alternatives to penicillins may be less effective, more toxic, and more expensive. Therefore, we used decision analysis to calculate maximum expected utility and minimum cost for skin-testing or not skin-testing patients who have endocarditis due to Staphylococcus aureus that is susceptible to cloxacillin and who have a questionable history of immediate-type hypersensitivity to penicillin. We used known probabilities of intermediate outcomes, actual costs, and measured utilities and included one-way sensitivity analysis. Whether utility, cost, or average cost-utility was the outcome of interest, skin-testing was preferred to no skin-testing in most conditions. Patients who have endocarditis due to S. aureus that is susceptible to cloxacillin and who also have a questionable history of immediate-type hypersensitivity to penicillin should be skin-tested before starting antibiotic therapy.