Introduction. Soft tissue injuries of the lower extremity are the result of high-energy trauma, such as road accidents, and remain challenging for most orthopedic surgeons. Proper selection of the treatment is important considering the risk of delayed necrosis and wound sepsis. Negative pressure wound therapy (NPWT) has improved complex wound treatment since 1997, but all treatments present advantages and limits. Case Report. A 21-year-old male presented with a high-energy soft tissue injury of the lower extremity. Three days after surgical debridement, complete skin necrosis developed. Successive surgical debridement was done in combination with traditional NPWT for 2 weeks; yet the wound did not progress toward healing, and the bone remained exposed. Negative pressure wound therapy with instillation and dwell time (NPWTi-d) was used with a novel reticulated open cell foam dressing (ROCF-CC) because further surgical debridement was not possible, and the use of NPWT was not recommended by the French high authority for health. Growth of granulation tissue was fast (9 days), even over the bone, without any surgical debridement and despite the presence of nonviable and fibrinous tissue. After that, traditional NPWT was discontinued and a split-thickness skin graft then was used to cover the defects. Four weeks following the accident, all wounds were completely healed. Conclusions. Surgical debridement remains irreplaceable; however, when debridement is not feasible, NPWTi-d with ROCF-CC might be the treatment of choice. This strategy allowed the authors to ensure coverage of an extensive loss of soft tissue when the traditional NPWT limit was reached.