Staphylococcus lugdunensis, a coagulase-negative staphylococcus, is being increasingly recognized as the cause of serious infections. We report 2 cases of total knee arthroplasty infection caused by S lugdunensis. S lugdunensis frequently produces a clumping factor that can result in a positive slide (short) coagulase test result. If the microbiology laboratory does not use the tube coagulase (long) test to confirm the slide coagulase test result, the organism may be misidentified as Staphylococcus aureus. S lugdunensis is more virulent than other coagulase-negative staphylococci and in many clinical situations behaves like S aureus, further increasing the confusion. However, S lugdunensis differs from S aureus in that it is susceptible to most antibiotics. This fact may alert the microbiology laboratory or the clinician that the isolate is likely not S aureus and prompt further testing of a specific isolate. Accurate identification of S lugdunensis isolates facilitates studies to define the epidemiology and pathogenesis of prosthetic joint infection due to S lugdunensis and delineates optimal medical and surgical therapies.