Background: Soft tissue defects of the limb with exposure of tendons and bones in critically ill patients usually lead to extremity amputation. A potential treatment with topical negative pressure may allow split-thickness skin grafting to the bone, which leads to limb salvage.Materials and Methods: We report on 21 multimorbid patients, 46 to 80 years of age, with severe lower limb soft tissue loss and infection with exposed bone following debridement with critical limb ischemia. Attempts to salvage the extremities were undertaken with repeated surgical debridement followed by vacuum-assisted closure therapy and subsequent split-thickness skin grafting procedures.Results: Infection control and limb salvage were achieved in all cases with multiple debridements, topical negative pressure therapy, and skin grafts. In all patients, the exposure of tendons and bones was reversible by this strategy without a free flap transfer.Discussion: The patients described in this study were severely compromised by systemic and vascular disorders, so extremity amputation had been considered owing to the overall condition and the exposure of tendons and bones. Since it was possible to salvage the affected limbs with this straightforward and simple procedure, this type of treatment should be considered as a last attempt to prevent amputation.