Project Summary/Abstract Patients with penicillin allergies receive toxic antibiotics that place them at higher risk for adverse events, including surgical site infections. However, most patients who report a penicillin allergy can tolerate penicillins and other beta-lactam style antibiotics without any problems. One large healthcare system silenced low risk penicillin alerts without increasing adverse events for patients. BJC HealthCare, our 14 hospital network headquartered in St. Louis, MO, silenced low risk penicillin alerts in 2019 based on these findings. We have been able to demonstrate that silencing low risk penicillin allergy alerts was also safe in our healthcare system. For this project, we propose to evaluate the impact silencing low risk penicillin allergy alerts for surgical patients in our healthcare system. We hypothesize that removal of the alert will be associated with an increase in cefazolin prescribing for common surgeries via an interrupted time series analysis. We also hypothesize that the removal of the alert will be associated with a reduction in surgical site infection rates among penicillin allergic patients but not control (non-penicillin allergic) patients using an interrupted time series analysis. We believe that this project aligns well with the mission of AHRQ to “produce evidence to make healthcare safer, higher quality, more accessible, equitable, and affordable, and to work within the U.S. Department of Health and Human Services and with other partners to make sure that the evidence is understood and used.” Indeed, this intervention to silence low risk penicillin allergy alerts would be scalable in any healthcare system without requiring any additional resources. If effective, this simple intervention could be easily added to existing AHRQ toolkits or provide preliminary data for a large pragmatic prospective multicenter study. This is unique among most research projects, as implementation of new innovations requires substantial investment among healthcare systems that often have limited resources. We are well suited to complete the proposed work. All of the proposed data has already been collected during routine patient care. We already have IRB approval, and we have collected much of it prior to grant submission. For the remaining steps, we have assembled an outstanding team of investigators that includes leaders in infection prevention, antimicrobial stewardship, allergy/immunology, and biostatistics. These individuals have a strong track record of collaborating, obtaining extramural funding, and completing their proposed research projects.