Background: Vacuum-assisted closure therapy has gained widespread use since its introduction in 1997. Previous studies have attributed significant benefit to its use for treatment of sternal wounds with or without mediastinitis. Management of sternal wounds with this therapy has been shown to decrease the number of dressing changes, reduce the time between debridement and definitive closure, and reduce costs associated with a protracted course of in-hospital dressing changes. The therapy has been used both as a bridge between debridement and definitive closure and as a catalyst to secondary sternal-wound healing. Methods: The authors performed a retrospective review of 103 patients who underwent vacuum-assisted closure therapy after median stemotomy between June of 1999 and March of 2004 at a single institution. The wounds were classified as sterile wounds, superficial sternal infections, and mediastinitis. The wound closure device, consisting of a polyurethane sponge and evacuation tube with inline suction, was applied sterilely to all wounds over a layer of Acticoat. Results: Vacuum-assisted closure was utilized in the treatment of sternal wounds for 103 patients (67 male patients and 36 female patients) whose mean age was 52 years (range, 3 months to 91 years). Patient comorbidities included diabetes, chronic obstructive pulmonary disease, end-stage renal disease, immunosuppression, and others. Sixty-four percent of the patients had a diagnosis of mediastinitis; 36 percent had either superficial infections or a sterile wound. The therapy was utilized for an average period of 11 days per patient. Sixty-eight percent of the patients (70 of 103) had definitive chest closure with open reduction internal fixation and/or flap closure. The remaining 32 percent had no definitive closure method. The overall mortality rate was 28 percent (29 of 103 patients), although no deaths were directly related to use of the therapy, and only four deaths resulted from sepsis as a consequence of mediastinitis. Conclusions: The authors report the largest series of patients treated with this therapy for post-sternotomy sternal wounds and believe it is safe and effective as a first-line therapy in the management of sternal wounds. The mortality rate from their study represents the patients' underlying disease process and comorbidities and is not a reflection of complications associated with the therapy. Vacuum-assisted closure therapy has been shown to decrease wound edema, decrease the time to definitive closure, and reduce wound bacterial colony counts. The authors have implemented the therapy for most patients with sternal wounds/mediastinitis at their institution, and believe it should be a standard protocol in the first-line management of these types of wounds.