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Background: Deep sternal wound infection is a serious and expensive complication after cardiac surgical procedures. We tried to identify risk factors for failure of vacuum-assisted sternal closure and compare the outcome and long-term quality of life (QoL) with the results obtained after sternal resection and muscle flap., Methods: Between January 1998 and December 2003, 5,690 patients underwent cardiac surgical procedures at our institution. Fifty-five patients who had deep sternal wound infection were identified between January 1998 and December 2003. In-hospital data were assessed and the outcome was analyzed. QoL, using the Short Form 36 Health Survey Questionnaire (SF-36), was assessed and an additional questionnaire focused on specific problems., Results: Overall mortality was 5.4%. Patients with successful vacuum-assisted sternal closure were younger and had fewer cumulative risk factors (chronic obstructive pulmonary disease, bilateral internal mammary artery, obesity, diabetes), than patients in whom secondary closure failed. Quality of life was better among patients with secondary vacuum-assisted closure than among patients with musculocutaneous flap. Independently of the modality of treatment, pain was not a serious problem reported by the patients during the follow-up., Conclusions: We conclude that preservation of the sternum should be the principal aim of surgical treatment in patients with deep sternal wound infection. Early diagnosis, aggressive surgical treatment by débridement, and the use of vacuum-assisted systems allows us to achieve a good long-term result with nearly normal QoL. Resection and musculocutaneous flap is a therapeutic option for high-risk patients, providing a safe, effective control of the infection, and it leads to acceptable results in terms of pain control and QoL.