ABSTRACTObjective: This decision-analytic study was intended to determine the expected cost-effectiveness of linezolid compared to vancomycin for treating surgical site infections (SSIs) caused by methicillin-resistant Staphyloccocus aureus (MRSA) from the perspective of a tertiary-care academic medical center.Research Design and Methods: This study is a cost-effectiveness analysis based on a modeling approach for the treatment of MRSA SSIs. Three clinical scenarios were considered in the decision analysis: (1) treatment with intravenous (IV) vancomycin during hospitalization and after discharge with home-care follow-up; (2) treatment with IV vancomycin during hospitalization, followed by oral linezolid after discharge; (3) treatment with oral linezolid during hospitalization and after discharge. Cost data was obtained from internal and external sources. Cure rate probabilities for MRSA SSIs were obtained from records at the medical center and from results of a randomized, multicenter trial. Healthcare costs for each scenario were obtained from the medical center, healthcare buying groups, and national databases. The robustness of the baseline cost-effectiveness determination was evaluated using sensitivity analyses over a broad range of costs and probabilities.Results: Treatment with oral linezolid during hospitalization and after discharge (scenario 3) was associated with lower costs ($8923, $11 479, and $12 481, respectively) and greater effectiveness (0.867, 0.787, and 0.707, respectively) compared to the IV vancomycin/oral linezolid switch (scenario 2) and IV vancomycin (scenario 1), so it dominated the latter options in the base-case, incremental cost-effectiveness analysis ($10 292, $14 486, and $17 653 per MRSA SSI cure, respectively). Furthermore, the sensitivity analysis demonstrated that the IV vancomycin/oral linezolid (scenario 2) option would be the expected cost-effective choice only if the length of hospitalization for this scenario was less than 6 days or if the probability of cure with oral linezolid (scenario 3) was less than or equal to 0.72; otherwise, the oral linezolid option was dominant. A major limitation of this study is the utilization of probability estimates from both institutional and published research sources. Additionally, the success rates for linezolid were obtained from one relatively small randomized, open-label trial.Conclusions: Using decision-analytic modeling, treatment with oral linezolid during hospitalization and after discharge is expected to be the most cost-effective approach for treating SSIs caused by MRSA.