A collection of 99 staphylococcal isolates associated with prosthetic joint infection and 23 coagulase-negative taphylococci isolated from noninfected arthroplasty-associated specimens were screened in order to determine whether the presence of icaA could be used to distinguish between pathogens and nonpathogens. All Staphylococcus aureus prosthetic joint infection isolates (n = 55) were icaA positive. A total of 46% (20 out of 44) of coagulase-negative staphylococcal prosthetic joint infection isolates were icaA positive, and 30% (7 out of 23) of arthroplasty-associated non-prosthetic joint infection-associated coagnlase-negative staphylococcal isolates were icaA positive (P = 0.23). Certain coagulase-negative Staphylococcus species appeared more likely to be isolated as either arthroplasty-associated non-prosthetic joint infection-associated isolates (e.g., Staphylococcus warnen and Staphylococcus hominis) or pathogens (e.g., Staphylococcus lugdunensis). The presence of icaA in a coagulase-negative staphylococcal isolate associated with an arthroplasty is not a useful diagnostic indicator of pathogenicity.