A prospective, single-centre, randomized controlled study was performed to evaluate the effectiveness of Graftjacket, a human acellular regenerative tissue matrix as a treatment option for chronic non healing lower extremity wounds. Twenty-eight diabetic patients with full-thickness wounds that had been present for at least 6 weeks were treated with sharp debridement and randomized to a single application of Graftjacket tissue matrix plus mineral oil-soaked fluff compression dressing or to a control treatment of wound gel with gauze dressings. All patients were seen weekly. By week 16, 12 of 14 patients treated with Graftjacket tissue matrix demonstrated complete wound closure compared with 4 of 14 patients in the control group. Patients treated with Graftjacket tissue matrix showed a statistically significant higher percentage of wound healing with respect to wound area, and clinically significant differences in wound depth and wound volume. This comparison is not performed to demonstrate that the application of the Grafjacket is more effective than sharp debridement. This study is done to help assign a role to the use of Graftjacket matrix in lower extremity wound care.