BACKGROUND: Comparisons of different staphylococci in orthopedic implant infections have rarely been reported. In this study we assessed total joint arthroplasty infections and other orthopedic implant infections due to methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and coagulase-negative staphylococci (CoNS). METHODS: This was a retrospective study performed at the Geneva University Hospitals for the period January 1996 to June 2008. RESULTS: There were 44 infections due to MRSA, 58 due to MSSA, and 61 due to CoNS. Overall cure was achieved in 57% (25/44) of MRSA infections, 72% (42/58) of MSSA infections, and 82% (50/61) of CoNS infections, after a minimum follow-up of 1 year. In the subgroup of arthroplasty infections only, cure was achieved in 39% (7/18) of MRSA, 60% (15/25) of MSSA, and 77% (30/39) of CoNS episodes. In multivariate analysis, arthroplasty (odds ratio (OR) 0.2, 95% confidence interval (95% CI) 0.1-0.6) and MRSA infections (OR 0.3, 95% CI 0.1-0.9) were inversely associated with overall cure for all implants. CoNS infection (OR 3.0, 95% CI 1.2-8.0) and the insertion of a new implant (OR 4.5, 95% CI 1.6-13.1) were associated with higher cure results. Methicillin resistance, immunosuppression, sex, age, duration of antibiotic therapy, one-stage revision, rifampin use, and total number of surgical interventions did not influence cure. MRSA-infected patients had more post-infection sequelae than patients with MSSA or CoNS (Chi-square test 13/44 vs. 93/119, OR 3.4, 95% CI 1.3-8.9, p=0.004). CONCLUSIONS: In orthopedic implant infections, S. aureus is more virulent than CoNS. MRSA has the worst outcome and CoNS the best.