Negative pressure wound therapy using vacuum-assisted closure (VAC) devices is currently a well established technique for managing complicated wounds. Such wounds occur after aggressive surgical debridement for necrotizing soft tissue infections (NSTI). In this report we present our experience in two intravenous drug abusers managed with VAC for NSTIs. The patients were 25 and 34 years old, HCV positive and presented with oedema of the upper femoral compartments and concomitant severe sepsis. Ultrasonography and computed tomography revealed severe cellulitis, fluid collection and necrosis of the affected fasciae and muscles. After emergent and subsequent aggressive surgical debridement during the first 48h, the VAC device was applied. Both patients had an uncomplicated postoperative course and a fast recovery from their multiorgan dysfunction. Suture closure of the wounds was achieved at the 25th and 38th postoperative days respectively and patients were discharged without any motor deficit. Negative pressure wound therapy is a modern therapeutic modality for treating complicated infected wounds. Moreover, it accelerates wound healing and primary closure, facilitating patient ambulation and recovery. A dedicated medical and nursing team is an important prerequisite for a successful outcome.