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Aim. The primary aim of this quality improvement project was to assess compliance with BOAST4 guidelines for the delivery of antibiotic prophylaxis in patients presenting to a major trauma centre with open limb fracture and evaluate the impact of implemented changes on attainment of these guidelines. Secondary aims were to assess adherence to local guidelines for the type of antibiotic prescribed. Method. A multi-cycle audit and quality improvement project was carried out for all patients presenting to Brighton and Sussex University Hospitals NHS Trust (BSUH) with open limb fractures from 1st September 2018 to 31st January 2019, and 1. st. November 2019 to 31. st. March 2020. Patients were identified through retrospective screening of electronic operation records (Bluespier) by authors, and paper records were subsequently reviewed for data pertaining to antibiotic prescriptions. Following the initial audit cycle, targeted teaching was carried out for orthopaedic trainees, new posters were placed in key clinical areas to highlight local guidelines, and alterations to the trauma clerking proforma were implemented, to include BOAST4 guidelines. Results. In cycle 1, a total of 52 patients received surgical treatment for open limb fractures, of which 48 (92.3%) were prescribed antibiotics prior to definitive management, with a mean time to administration of 271 minutes. Of these, 41 (78.8%) received prescriptions according to BSUH guidelines. The use of STAT prescriptions was found to significantly reduce the mean time to administration from 298 minutes to 144 minutes (p = 0.044). In cycle 2, a total of 29 patients received surgical treatment for open limb fractures, of which all 100% were prescribed antibiotics prior to definitive management, with a reduced mean time to administration (233 minutes). Of these, 26 (89.7%) received prescriptions according to BSUH guidelines, and a significantly greater proportion (p = 0.0003) received initial STAT ‘once-only’ prescriptions (51.7% vs. 15.4%). Conclusions. This quality improvement project has demonstrated the successful implementation of targeted changes to improve the attainment of BOAST4 guidelines. Following a multi-cycle audit, all patients now receive antibiotic prophylaxis, with a higher proportion receiving antibiotics according to local BSUH guidelines. Furthermore, the use of STAT ‘once-only’ prescriptions, which was shown to be beneficial during the first audit cycle, has now significantly increased following intervention