BACKGROUND: Distal femur replacement (DFR) with a stemmed megaprosthesis represents a challenge due to high rates of loosening and limited reconstructive options if the implant fails. Such an unfavourable scenario is even more complex where there are also infected bone defects. The Compress® device was developed to provide an alternative to traditional intramedullary stems. We report on the outcomes of a staged protocol using the Compress® DFR, protected with a vancomycin-gentamicin-loaded hydrogel, in infected non-oncological scenarios. METHODS: Retrospective longitudinal cohort study including patients with infected defects of the distal femur following orthopaedic trauma or periprosthetic joint infection (PJI) and managed with the protocol described. Protocol features, microbiological data, radiological results, complications, infection control, and implant survivorship were assessed. Minimum follow-up was 18 months or until implant removal. RESULTS: 21 cases of Compress® DFR were included. On average, patients had 4.9 prior surgeries and 14.5 cm distal femur bone defects after pseudo-oncological resection. After median follow-up of 42 months (18-83 months), no infection recurrence occurred
limb salvage was achieved in all cases. Five patients experienced aseptic loosening, all within the first 7 post-operative months. Beyond this time threshold, no further implant failures were observed, resulting in a cumulative implant survival rate of 75% at 1 and 5 years, and of 75% at final follow-up. CONCLUSION: Staged Compress® DFR with antibiotic-loaded hydrogel protection is a reliable option for selected patients with distal femoral bone defects, offering high infection control, durable implant survivorship, and simplified revision. Aseptic failures occurred primarily within the early post-operative months, highlighting the need for close monitoring during this critical period. This approach provides a promising solution for complex non-oncological cases involving infected distal femoral bone defects.