The preferred treatment for incisional hernias occurring post laparotomy involves use of prosthetic mesh. If this mesh becomes infected, it may have to be removed to achieve wound healing. A patient with a methicillin-resistant Staphylococcus aureus-infected prosthetic mesh received negative pressure wound therapy to help facilitate healing without removing the prosthetic mesh applied to manage his hernia. After almost 4 weeks of treatment, the wound was closed secondarily. The literature contains many case studies about the use of NPWT for a variety of wounds but information about its safety and effectiveness for managing methicillin-resistant Staphylococcus aureus-infected prosthetic mesh is limited. The results of this case study add to the evidence that controlled clinical studies are warranted.