Treating chronic wounds of the lower extremity with underlying osteomyelitis remains challenging. When standard local wound therapy modalities fail, and salvageable treatment options are exhausted, debridement of infected bone and soft tissue with flap coverage augmentation can be a consideration prior to amputation. We propose the first article in the literature on monitoring inflammation labs for resolution of osteomyelitis with reconstructive approach in limb salvage by harvesting muscle flap for coverage of soft tissue deficits overlying resected infected bone. The evaluation of successful outcome is determined by wound closure with resolution of elevated inflammatory labs in a case-control study. Three patients were retrospectively analyzed and successful outcome was achieved in all cases in a short-term follow-up of 16 months. Muscle transpositional flaps should be considered as an alternative salvage procedure prior to amputation.