The most widely used techniques for graft preservation after localized graft infections are muscle flap closure or antibacterial dressings and irrigations after débridement. Vacuum assisted closure (VAC) has been increasingly used for complex wounds in vascular surgery, including groin infections, but not directly on exposed bypass grafts as a stand-alone technique. We used the VAC system after wound débridement in four patients with fully exposed synthetic bypass grafts who were too unstable or risky for further operative interventions. Mean duration of VAC use was 22.8 days (range, 6 to 53 days), with time to total wound closure of 30 to 63 days (mean, 41 days). There were no reinfections with 11 to 25 months' follow-up (mean, 18.3 months). For high-risk surgical patients with a fully exposed infected prosthetic vascular graft, VAC therapy along with aggressive débridement and antibiotic therapy may be an effective alternative to current management strategies.