Background: The purpose of our study was to determine the efficacy of a management algorithm that includes negative pressure wound therapy (NPWT) in diabetic feet with limb-threatening infection. Materials and Methods: Forty-five septic diabetic feet were treated with NPWT between 2006 and 2008. After emergent abscess evacuation, early vascular intervention was performed if necessary. Debridement, with or without partial foot amputation, was followed by NPWT. Wound progress was measured using a digital scanner. A limb was considered salvaged if complete healing was achieved without any or with minor amputation through or below the ankle. The mean followup after complete wound healing was 17 (range, 6 to 35) months. Results: Thirty-two cases (71%) were infected with two or more organisms. Negative pressure wound therapy was applied for 26.2 ± 14.3 days. The median time to achieve more than 75% wound area granulation was 23 (range, 4 to 55) days and 104 (range, 38 to 255) days to complete wound healing. Successful limb salvage was achieved in 44 cases (98%); 14 (31%) without any amputation and 30 (67%) with partial foot amputations. Total number of operations per limb was 2.4 ± 1.3. One case of repeated infection and necrosis was managed with a transtibial amputation. There were no complications associated with NPWT. Conclusion: This study provides the outcome of a management algorithm which includes NPWT in salvaging severely infected diabetic feet. With emergent evacuation of abscess, early vascular intervention and appropriate debridement, NPWT can be a useful adjunct to the management of limb-threatening diabetic foot infections. Level of Evidence: IV, Retrospective Case Series