BACKGROUND: Open fracture wounds are associated with a high risk of infection, though the outcomes are dependent on the fracture location, prophylactic antibiotics utilized, and time to antibiotic intervention. Although several institutions have provided guidelines for appropriate prophylaxis in open fractures, there is currently no consensus on antibiotic selection and duration. Reducing inappropriate prophylactic antibiotic use for open bone fractures is a potential stewardship opportunity within pharmacy departments. OBJECTIVES: This study aimed to determine the rates of open fracture-related infections and antibiotic ordering adherence to institutional guidelines. Patients were grouped based on the time of diagnosis relative to the institutional change that occurred in March 2016. The primary outcome was the 60-day incidence. Methodology: This was a retrospective chart review of patients from July 1, 2014, to November 30, 2018. Patients were assigned to either a pre-implementation or a post-implementation group based on the time of open fracture diagnosis. One hundred fifty patients were randomly selected, and 75 were assigned to each group. Patient encounters were evaluated for demographics, open fracture site, Gustilo-Anderson grade, infective organisms, protocol use, prophylactic antimicrobials, infection occurrence, duration of therapy, surgical intervention, provider specialty, and length of stay. Results: One hundred ninety-nine patients were screened while 150 were included in the final analysis. We found a 6.7% incidence of infection in the pre-implementation group and a 5.3% incidence in the post-implementation group within 60 days of the open fracture. Infection rates at 12 months increased to 9.3% in the pre-implementation group and 6.7% in the post-implementation group. Fewer than 50% of open fractures among all patients received a documented fracture grade. Conclusion: Updates to our institutional antibiotic guidelines for open fractures did not significantly reduce infection rates, likely due to low adherence and insufficient fracture grading documentation. Future efforts should focus on improving compliance and establishing consensus guidelines to optimize infection prevention.