Introduction: The vacuum-assisted closure (V.A.C.(R))-therapy is accepted for an efficient option in the treatment of infected wounds with healing complications. However, reports on its use in the septic orthopedic surgery are seldom. Hence, the aim of this study is to demonstrate our experience with the V.A.C.(R)-system in the treatment of orthopedic-related infections. Patients-Methods: Various musculoskeletal infections with prolonged wound healing (infections after Achilles tendon reconstruction, fibula osteosynthesis, dorsal spondylodesis, and total hip arthroplasty, skin necrosis after total knee arthroplasty and wound dehiscence after resection and irradiation of a liposarcoma) have been treated with the V.A.C.(R)-device. After infection sanitation we performed skin graft transplantation in 3 cases for definitive wound closure, also assisted by the V.A.C.(R)-therapy. Results: An infection eradication with implant preservation, where necessary, could have been achieved in all cases. No complications were observed in the cases with the skin graft transplantations. No infection persistence or reinfection occurred at a mean follow-up of 36 months. Discussion: The V.A.C.(R)-therapy seems to be a valuable adjunct in the treatment of infected wounds in the orthopedic surgery, however, definitive conclusion should await the results of future clinical studies with large series.