Purpose. An initiative to determine the effects of penicillin skin testing (PST) from an antimicrobial stewardship perspective is described. Summary. Penicillin allergy is one of the most frequently reported altergies; however, only about 10% of self-reports of penicillin allergy are accurate. Incorrect penicillin allergies are therefore a significant barrier to antimicrobial stewardship, with important clinical and economic implications, including increased antimicrobial resistance, an increased overall cost of care, increased length of stay, and, ultimately, increased mortality. As part of its antimicrobial stewardship program, a community health system launched a PST initiative in order to optimize therapy, reduce adverse events acquisition costs, and minimize development of antibiotic resistance. The PST prograit involves the use of a standardized protocol for the assessment of hypersensitivity to penicillin in patients with suspected penicillin allergy. Among 36 patients who completed the PST protocol during an eight-month period, all had a negative result; in 27 of those patients, a conversion of antimicrobial therapy to a penicillin or cephalosporin was implemented as a direct result of PST. Conclusion. In patients with a self-reported penicillin allergy, PST led to a reduction in the use of carbapenems, aztreonam, vancomycin, and other broad-spectrum agents within a health system. A decrease in drug costs was documented in a sample of patients switched to a penicillin or a cephalosporin after PST.