Beta-lactams provide superior outcomes in comparison to vancomycin in treating methicillin-susceptible Staphylococcus aureus (MSSA) infections complicated by bacteremia. However, approximately 11% of inpatients report a penicillin (PCN) allergy when it is estimated that only 1% of the general population is truly allergic to the antibiotic. Consequently, many patients may be receiving suboptimal treatment for a serious infection with a high mortality rate. This study evaluated the cost-effectiveness of penicillin skin testing (PST) in adult inpatients self-reporting PCN allergy and undergoing treatment for MSSA bacteremia. A decision analytic model was developed comparing an acute care PST intervention to a scenario with no confirmatory allergy testing. This dataset includes a decision analytic model diagram, model inputs, and an Excel file with MSSA bacteremia model parameters and probabilistic simulation calculations.