A foot ulcer due to diabetes and/or arteriosclerosis obliterans (ASO) frequently results in an intractable condition that resists treatment. To cope with this condition, we have developed a combination therapy that includes conventional conservative therapy plus surgical therapy. This aggressive conservative therapy using aggressive debridement, trafermin (Fiblast Spray, Kaken, Japan) treatment and vacuum-assisted closure (VAC) therapy was adopted to treat seven patients suffering from diabetes and ASO-related refractory foot ulcer accompanied by bone exposure. With the exception of one patient who died during the treatment, the remaining six patients obtained limb salvage. The mean time to cure was 8.3 months. This approach should be considered before amputation. Some patients may refuse amputation or cannot tolerate highly invasive surgical treatment including tissue transplantation. In such cases, this aggressive conservative therapy can be employed as a highly useful and reproducible technique requiring simple techniques.