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Introduction Contemporary conflict-associated injuries with open fractures are challenged by infection and antimicrobial resistance (AMR), compromising empiric antimicrobials and limiting options for systemic treatment. Local antimicrobials in high concentrations may offer an adjunctive therapy but the evidence and its relevance to conflict settings are unclear.Methods A systematic review was undertaken using the Medline, Embase and Cochrane databases, searching for evidence relating to the use of local antimicrobials to prevent infection after extremity open fracture. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The review considered evidence for the effect of local antimicrobials across different agents, different causes of infection, AMR and adverse effects. Available evidence was considered in the context of its relevance to conflict injuries and priority research gaps were identified.Results No studies were identified in conflict or humanitarian settings. Seven civilian systematic reviews and meta-analyses considering different outcomes and four randomised controlled trials (RCTs) were identified. There was low-quality evidence for a reduction in infection when using prophylactic local antimicrobials in addition to systemic antimicrobials, and there was no evidence of adverse outcomes. Evidence skewed towards use for Gram-positive infections. There was a lack of level one evidence and marked heterogeneity across study designs.Conclusion AMR has emerged as a major challenge for the management of open fractures sustained in conflict. There is an urgent requirement to identify alternative treatment options and adjuncts. Local antimicrobials and biomaterials present potential opportunities. Further evidence from RCTs is required across all settings. In the context of conflict, this must include relevant outcomes, including the impact of delayed surgery, wound contamination and AMR.