Prosthetic joint infections are a serious complication of prosthetic joint implantations. These infections are generally caused by gram-positive, aerobic pathogens, however anaerobic organisms have been rarely implicated. We describe the case of an adult male who developed a Clostridium perfringens prosthetic joint infection four weeks following a right total knee arthroplasty. The patient had recently had a revision of a vascular graft, and there was initial concern for infectious graft involvement. Our case highlights a successful management pathway that included staged surgical revisions and extended courses of clindamycin and metronidazole, which ultimately spared any vascular complications.