Background: Commercially available human placental amnion/chorion tissue allografts have been successfully used as protective treatment barriers for wounds and diabetic ulcers. Burn and traumatic limb injuries with exposed bone or tendon generally require surgical flaps or amputations for healing. The purpose of this study was to determine if dehydrated human amnion/ chorion membrane allografts (dHACM) with decellularized human collagen matrix (dHCM) could be used to salvage injured human extremities. Methods and Materials: dHACM/dHCM was topically applied to the wounds after debridement. Negative Pressure Wound Therapy (NPWT) was concurrently initiated, primarily to bolster the tissue with moisture and contamination control. Approximately every seven days, wounds were re-evaluated for granulation tissue growth response. As needed, patients received dHACM/ dHCM and NPWT in the outpatient or home care settings after discharge. Results: Fifteen males and two females (26 extremities) were treated for fourteen burn and three Necrotizing Soft Tissue Infections (NSTI) injuries. Closure was observed in patients after two to five dHACM/dHCM applications. The dHACM/dHCM treatment was initiated: (median) 17-days after injury; NPWT for 17-days; autograft or primary closure after 21-days; discharge 25-days after the first application. Conclusion: Treatment with human placental-derived allografts provided a protective covering that enabled the healing cascade to generate granulation tissue formation in extremity wounds with exposed tendon and/or bone. In select limb salvage cases, dHACM/dHCM treatment may be a promising alternative to amputations, tissue rearrangements, free tissue flaps or other techniques for resolution of extremity wounds with bone and tendon exposure.