Stenotrophomonas maltophilia is a well-known opportunistic Gram-negative bacterium causing mainly hospital-acquired infections, which rarely affects the musculoskeletal system. We report the first case, to our knowledge, of a periprosthetic infection caused by this pathogen in an artificial joint. Stenotrophomonas maltophilia has the ability to form biofilm, and subsequently should not be excluded in the investigation of prosthetic joint infections. Management in the establishment of such an infection demands aggressive operative treatment in conjunction with the proper antibacterial administration.