Aim: There is lack of evidence on the optimal duration of antibiotic prophylaxis following free-flap reconstruction in head and neck cancer. This review synthesizes the current evidence regarding antibiotic prophylaxis duration and its effect on surgical site infection (SSI) rates. Methods: Major databases such as PubMed and ScienceDirect were searched. Data from systematic reviews, meta-analyses and retrospective cohort studies were summarized and critically appraised. Key outcomes were included – SSI rate, antibiotic-related adverse events and flap complications. Results: Several studies suggest that a prophylaxis duration of 24 hours or less may be adequate in clean-contaminated head and neck free-flap cases. A meta-analysis (n= 861) found no statistical significance of a higher SSI risk when antibiotics are given for < 24h in comparison to >24. A large retrospective cohort study (n=427) found no independent benefit of extended duration over 24h. The majority of studies highlight that antibiotic choice appears to affect SSI rates more than the duration of perioperative antibiotic prophylaxis. Limitations of the study designs included - discrepancies in the definition of short vs long duration, level of contamination, patient population and risk factors. Conclusion: Current literature suggests that prolonged antibiotic therapy (>24h) following free-flap reconstruction in head and neck cancer may not guarantee a reduced SSI risk. Emphasis on appropriate antibiotic choice, patient risk-profiling and surgical technique should be considered when deciding on appropriate antibiotic duration. Further prospective trials focusing on free-flap head and neck reconstruction are needed to evaluate optimal antibiotic duration stratified by flap type, patient risk-factors and reconstructive complexity. References 1. Mitchell RM et al. Antibiotic Prophylaxis in Patients Undergoing Head and Neck Free Flap Reconstruction. JAMA Otolaryngol Head Neck Surg 2015; 141:1096-1103.