Vacuum-assisted closure(VAC) therapy is mainly used for tissue defects. VAC therapy can remove exudate that could impair the healing process. We applied VAC therapy in patients considered at high risk of surgical site infection who underwent cardiovascular surgery via standard median sternotomy. Risk factors included advanced heart failure, obesity, diabetes mellitus, steroid administration, immunosuppressant administration, and chronic renal failure, etc. VAC therapy was used in 134 patients. Only 3 of these patients (2.2%) developed surgical site infection caused by Staphylococcus epidermidis;2 patients fully recovered after prolonged VAC therapy for 2 weeks, and the other required an additional sternal fixation after the sternal wires were removed for wound infection control. No patient developed infective mediastinitis. Prophylactic VAC therapy can reduce postoperative wound infection in high risk patients undergoing open heart surgery via full sternotomy.