Background Although penicillin allergy is commonly reported, less than 1% of the population are truly allergic to penicillin. False penicillin allergy labelling may be associated with suboptimal antibiotic selection, greater costs, and higher prevalence of antibiotic-resistant organisms. The purpose of this study was to evaluate outcomes of implementing a pharmacist-led penicillin-allergy screening protocol on the antibiotic prescribing habits and the appropriateness of selecting first line antimicrobial therapy. Methods A retrospective, quasi-experimental study included 97 patients with suspected or confirmed common infections. Data was collected between January 2020 to August 2021 for the pre-protocol implementation group (PPG) and between November 2021 to April 2022 for the post-protocol implementation group (PPI). Adults ( > 18 years) with a documented penicillin allergy were included. Patients with penicillin allergy were identified and interviewed by our Emergency Department (ED) clinical pharmacists using an evidence-based algorithm. Data were analyzed using two-sample Student’s t-test and descriptive statistics. Results Fifty-one patients in PPG and 46 in PPI. In the PPG, 60.8% (31/51) had a history of beta-lactam tolerance and 26% (8/31) tolerated at least a penicillin derivative previously. While, twenty-two patients (47.8%) in the PPI tolerated beta-lactams and 50% (11/22) tolerated at least one penicillin derivative. Thirty-eight patients (82.6%) had a documented infection in the PPI and received an antibiotic. The use of Moxifloxacin was significantly lower in the PPI vs the PPG, 0% (0/38) vs 17.6 (9/51) respectively, (P=0.008). However, the use of ciprofloxacin, vancomycin, and aztreonam was lower in the PPI vs the PPG but was not statistically significant (Table 2). Antibiotic therapy appropriateness was higher in the PPI as compared to the PPG, 86.8% (33/38) vs 49% (25/51) respectively, (P=0.0004). In the PPI, documented penicillin allergies were delabeled in 23.9% (11/46) of patients. Conclusion We observed higher rates of appropriate first line antibiotic therapy selection post-implementation of the pharmacist led penicillin allergy screening protocol. This could be an effective strategy to optimize antimicrobial therapy in the hospital setting. Disclosures All Authors: No reported disclosures.