Background <p>Fracture-related infection (FRI) following lateral malleolus fracture fixation complicated by soft tissue breakdown represents a challenging clinical problem with no established standard of care. This study evaluates a treatment strategy consisting of prolonged antibiotic suppression until fracture union, followed by delayed single-stage surgical management.</p> Methods <p>This retrospective consecutive case series included 11 patients treated between 2020 and 2023 at a multidisciplinary orthopaedic infection unit. All patients were managed according to a standardized protocol involving oral antibiotic suppression until radiologically confirmed fracture consolidation. This was followed by a single-stage surgical procedure including implant removal, radical debridement, deep tissue sampling, local antibiotic therapy, and soft tissue reconstruction using a distally based peroneus brevis muscle flap with split-thickness skin grafting.</p> Results <p>Eleven consecutive patients (median age 58 years) were treated according to the protocol. Six patients underwent antibiotic suppression for a median duration of 147 days prior to surgery. Among patients available for outcome assessment, infection control was achieved in 10 of 10 surviving patients. One patient died of unrelated causes within 14 days postoperatively and was not classified as treatment failure. Soft tissue complications were common, with partial flap necrosis occurring in 4 patients (36%) and split-skin graft loss in 6 patients (55%), predominantly managed conservatively.</p> Conclusions <p>Delayed single-stage surgical management following prolonged antibiotic suppression may represent a feasible treatment strategy for selected patients with FRI after lateral malleolus fixation. However, the high rate of soft tissue complications and the limited sample size warrant cautious interpretation. Further comparative studies are needed to define the role of this approach.</p>