Abstract Background This study was performed to evaluate the results of negative pressure wound therapy (NPWT) in patients with open wounds in the foot and ankle region. Materials and methods Using a NPWT device, 16 patients were prospectively treated for soft tissue injuries around the foot and ankle. Mean patient age was 32.8 years (range, 3–67 years). All patients had suffered an acute trauma, due to a traffic accident, a fall, or a crush injury, and all had wounds with underlying tendon or bone exposure. Necrotic tissues were debrided before applying NPWT. Dressings were changed every 3 or 4 days and treatment was continued for 18.4 days on average (range, 11–29 days). Results Exposed tendons and bone were successfully covered with healthy granulation tissue in all cases except one. The sizes of soft tissue defects reduced from 56.4 cm² to 42.9 cm² after NPWT (mean decrease of 24%). In 15 of the 16 cases, coverage with granulation tissue was achieved and followed by a skin graft. A free flap was needed to cover exposed bone and tendon in one case. No major complication occurred that was directly attributable to treatment. In terms of minor complications, two patients suffered scar contracture of grafted skin. Conclusion NPWT was found to facilitate the rapid formation of healthy granulation tissue on open wounds in the foot and ankle region, and thus, to shorten healing time and minimize secondary soft tissue defect coverage procedures.