Prosthethic Joint Infection (PJI) is a severe complication following joint replacement. Late PJI can occur years after implantation by hematogenous seeding of a microbial agent. Staphylococcus xylosus is a coagulase-negative commensal of the human skin and rarely associated with opportunistic human infections. We report the rare case of a 70-year old Patient suffering from knee pain 18 years after primary Total Knee Arthroplasty. Microbiological sampling detected S. xylosus as causative agent. The patient was successfully treated with a two-stage implant exchange and antibiotic therapy using co-amoxicillin and rifampicin/cotrimoxazol. This case illustrates the ability of S. xylosus to cause late PJI and the importance of not letting coagulase-negative Staphylococci be routinely categorized as contaminants of microbiological samples.