Debridement and retention of the prosthesis was the initial treatment modality in 30 patients with 33 Staphylococcus aureus prosthetic joint infections (PJIs) who presented to the Mayo Clinic between 1980 and 1991. Treatment failure, defined as relapse of S. aureus PJI or occurrence of culture-negative PJI during continuous antistaphylococcal therapy, occurred in 21 of 33 prosthetic joints. The 1-year and 2-year cumulative probabilities of treatment failure were 54% (95% confidence interval [CI], 36%-71%) and 69% (95% CI, 52%-86%), respectively. A median of 4 additional surgical procedures (range, 1-9) were required to control the infection in the 21 prosthetic joints for which treatment failed. Prostheses that were debrided >2 days after onset of symptoms were associated with a higher probability of treatment failure than were those debrided within 2 days of onset (relative risk, 4.2; 95% CI, 1.6-10.3). These data suggest that debridement and retention of the prosthesis as the initial therapy for PJI due to S. aureus is associated with a high cumulative probability of treatment failure and that the probability of treatment failure may be related to the duration of symptoms.