Introduction: Vancomycin-resistant Enterococcus (VRE) infection of prosthetic joints is an unusual infection. When it does occur, it is difficult to treat, as treatment options are limited and often fraught with difficulties. Case Report: We present a case of a patient with a VRE-infected total knee arthroplasty that was treated with a two-stage revision along with six weeks of intravenous and intraarticular daptomycin with a good outcome. Conclusions: A protocol for treating VRE in prosthetic joint infections has yet to be established and further randomized controlled studies are warranted for the management of such infections.