There are currently no guidelines for splenectomy patient undergoing total joint arthroplasty. We present a case history of a 63-year-old man with a history of splenectomy that underwent a total knee arthroplasty with standard intravenous antibiotic prophylaxis. Two weeks postoperatively, he developed a prosthetic joint infection and followed the standard antimicrobial management with intravenous and oral antibiotics prior to having revision surgery. We propose that there are guidelines to properly manage these patients in the pre- and perioperative setting following an orthopaedic procedure.