Background. Wounds with exposed bone or tendon continue to be a challenge for wound care physicians, and there is little research pertaining to the treatment of these particular wounds with allograft skin. The purpose of this study was to evaluate the effectiveness and safety of a biologically active cryopreserved human skin allograft for treating wounds with exposed bone and/or tendon in the lower extremities. Methods. Fifteen patients with 15 wounds at a single hospital-based wound care center were included in the study. Eleven wounds had exposed bone, 1 wound had exposed tendon, and 3 wounds had exposed bone and tendon. Standard treatment principles with adjunctive cadaveric allograft application were performed on all wounds in the study. Results. In this study 14/15 (93.3%) of the wounds healed completely. The mean duration of days until coverage of the bone and/or tendon with granulation tissue was 36.14 (5.16 weeks) (range 5-117 days). Mean duration to complete healing of the wound was 133 days (19 weeks) (range 53-311 days). The mean number of grafts applied was 2. There were no adverse events directly related to the graft. Zero major amputations and 1 minor amputation occurred. Conclusion. This study found biologically active cryopreserved human skin allografts to be safe and effective in treating difficult wounds with exposed bone and/or tendon. To the authors’ knowledge, this is the largest study to date focused on the utilization of allograft skin as an adjunct therapy for lower extremity wounds with exposed tendon and/or bone.