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Open tibial fractures are common injuries after high-energy trauma such as road traffic accidents. Infection is one of the main complications of open fractures. Broad-spectrum antibiotics have been used for prophylaxis and treatment of infection in these fractures. The duration of antibiotic prophylaxis remains controversial, especially for the different types and grades of open fractures. No complete review, to date, has been performed of published studies to demonstrate the wide variety of duration of antibiotic use in practice to prevent infection, especially in open tibial fractures. The purpose of the present study was to review the evidence in the current data regarding the duration of prophylactic antibiotic administration in open tibial fractures and to identify the optimum duration of administration of antibiotics to minimize the risk of infection in these fractures. We reviewed and evaluated all published clinical trials claiming or cited elsewhere as being authoritative regarding the duration of prophylactic antibiotic use in open tibial fracture management. A large number of studies reported antibiotic prophylaxis in open fractures; however, only 8 met the inclusion criteria set out for our review. Only 1 randomized, double-blind, prospective study examined the duration of prophylactic antibiotic administration in open tibial fractures. That study suggested a short course of antibiotics is as effective as a long course in infection prophylaxis. The results of the present review highlight the need for a rigorous randomized, double-blind, multicenter trial to establish an agreed protocol for the optimal length of prophylactic antibiotic administration in open tibial fractures., (Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)