Objective: To evaluate the role of post-debridement cultures in the prevention of future infection following open fractures. Design: Retrospective Cohort Study and Literature Review. Setting: Division of Orthopaedic Surgery, Sultan Qaboos University Hospital, Academic and tertiary health care, Muscat, Oman. Participants: A total of 166 patients from a cohort study and 539 patients from the literature review with open fractures. There were 640 cumulative patients fit the inclusion and exclusion criteria. Intervention: Using predetermined inclusion and exclusion criteria, data on all open fractures were gathered from the electronic health system of a single institution between 2010 and 2019. PubMed and Embase electronic databases were also searched for relevant articles relating to post-surgical debridement culture and its correlation with future infection. Main outcome measures: Assessing the benefit, role of post-debridement cultures in the prevention of future infection following open fractures. Results: Combining the results of this retrospective cohort study and previously published data, there were 640 Gustilo-Anderson grades II and III open fractures which had post-debridement screening. Eighty-eight patients (13.8%) developed an infection, out of which 16 had positive post- debridement cultures (18.2%). Only four grew similar organisms at screening and infection stages, two of which had different antibiotic resistance patterns at the infection stage. Seventy-two fractures had negative post-debridement screening swabs (81.8%). Of the 59 (9.2%) fractures with positive screening only four (6.8% of the infected fractures) developed later deep infection. All these 59 cases had culture-guided antibiotic treatment, with or without surgical debridement. Conclusion: Although the bacterial growth of post-debridement cultures is low, post-debridement screening as part of a comprehensive management protocol may have a role in reducing deep infection in open fractures. This is particularly the case in Gustilo and Anderson type 3 open fractures, the risk of infection is high. The poor association between organisms isolated from screening and those from subsequent deep infection may mean that the later infective organisms have been acquired from a secondary colonisation source after the debridement. Level of evidence: III