BackgroundOne of the great challenges in the management of open fractures is postoperative infection with a higher incidence in Gustilo-Anderson type III fractures. Definitive management of such fractures in developing countries is usually with external fixators with its attendant complications such as deep fracture-related infection, non-union, and consequent increased re-operation rates. Recently, there has been a novel method of using antibiotic-cement coated implants such as intramedullary nails and locking plates in the treatment of infected non-unions with reported excellent outcomes. This protocol aims to describe the hypothesis, objectives, design and statistical analysis of a randomized control trial that compares the infection rate between the use of antibiotics-cement coated plate and external fixation in the management of Gustilo-Anderson type III long bone fractures. MethodsThis is a multicentre, open-label, parallel group, superiority, randomized, control trial. All patients with type III long bone fractures who present at the emergency department will be screened for enrolment and only those patients that meet the inclusion criteria will be registered for the study. Patients will be randomized using a centralized 24-hr computerized randomization system into two groups: antibiotic-cement coated plate group and the external fixation group. The primary outcome will be occurrence of infection at any time during the course of one year follow-up which will be counted once for each of the patients. The secondary outcomes are union rate, re-operation rate and change in Health Related Quality of Life (HRQoL) from baseline to end of follow-up. Analysis will be done using R (R Core Team, 2023) and Rstudio (Rstudio Team, 2023). DiscussionLiterature has shown that use of antibiotic-coated plate in the management of severe open long bone fractures is effective in reducing infection rate. A significant difference in infection rate with use of antibiotic-cement coated plate compared to use of external fixator for open fractures will be a welcome intervention in developing countries. Trial registrationThe study protocol is registered with ClinicalTrials,gov (NCT06193330)