Authors: Jimin Jun, PharmD; April Finnigan, PharmD, BCCCP; Natalie Atkin, DO; Stefan Leichtle, MD, MBA; Lois Lee, PharmD, BCPPS, BCIDP Learning Objective: Audience members will be able to describe how implementation of a health system-developed guideline promotes consistent, evidence-based prophylactic antibiotic selection and duration for open fracture injuries. Background/Objective: Recent literature reports variability in prophylactic antibiotic practices for open fractures despite guidelines and stewardship efforts. This study describes how an institutional guideline supports antimicrobial stewardship and patient outcomes. Methods: This retrospective analysis included patients treated at a single tertiary care hospital from January 2022 through May 2025. Of 500 participants who received prophylactic antibiotics for open long bone fractures, 186 were analyzed; those discharged within 72 hours or undergoing extremity amputation were excluded. The study evaluated antibiotic patterns before and after the implementation of the system guideline in May 2024. The primary outcome was days of therapy for prophylactic antibiotics. The secondary outcomes included time to targeted therapy, protocol adherence in the post-implementation group, and trauma site infection incidence. The primary outcome was reported as a median with interquartile ranges and analyzed using Mann Whitney U, with statistical significance defined as a p-value less than 0.05. Secondary outcomes were reported as descriptive statistics with statistics completed using a chi-square test. Results: The primary endpoint, median duration of therapy, was significantly shorter after the implementation of a standardized institution guideline, decreasing from 2 days pre-guideline to 1 day post-guideline. Median time to targeted therapy was similar between groups (12 minutes pre-guideline vs. 11 minutes post-guideline). Regarding safety outcomes, surgical site infections occurred in 9.7% of pre-guideline patients and 11.8% of post-guideline patients. Overall guideline adherence in the post-guideline group was 77.4%. Conclusions: This study demonstrates the antimicrobial stewardship impact of implementing a hospital guideline to standardize antibiotic prophylaxis for open fracture injuries. A concurrent reduction in broad-spectrum antibiotic utilization, particularly piperacillin–tazobactam, further supports its stewardship benefit. Findings highlight the need for improved standardization and monitoring strategies for type III injuries, where guideline noncompliance was most frequent. Self-Assessment Question: What practice gap can an institution-derived guideline for antibiotic prophylaxis in open fracture injuries primarily address? Self-Assessment Answer: a) Variability in timing of surgical intervention, b) Inconsistency in antibiotic duration and selection, c) Under-recognition of surgical site infections, d) Limited access to broad-spectrum antibiotics