OBJECTIVES: To evaluate the cost-effectiveness of linezolid, compared to teicoplanin, for serious gram-positive infections from a randomized trial, which showed that linezolid had superior efficacy especially in bacteremia (ICAAC 2001; L-1481), a trend toward shorter LOS (ECCMID 2002; O140) and lower mean adjusted total cost of treatment (SCCM 2003; 200). METHODS: Hospitalized patients from 6 European (n=227) and 7 South American (n=203) countries with serious gram-positive infections including pneumonia, complicated skin/soft tissue infections, or bacteremia were treated with linezolid (intravenous followed by optional oral) or teicoplanin (intravenous followed by optional intramuscular) for up to 4 weeks, followed by up to 3 weeks of observation. Investigator-assessed end-of-treatment success/failure was used to determine effectiveness, missing/indeterminate evaluations were either scored as failures or imputed using logistic regressions. Resource use during the 49-day study period was collected and costs were assigned using standard costing methods (converted to 2001 US$). Due to the nearly threefold between-continent cost difference, data were analyzed separately. Multivariate methods were used to adjust both cost and effectiveness for baseline variables. Probabilities of treatment benefits were estimated using bootstrap methods. RESULTS: The adjusted incremental total cost of treatment was $932 and $484 lower for linezolid; the adjusted incremental effectiveness was 5.8% and 6.4% higher with linezolid when missing effectiveness was scored as failures, or 12.3% and 4.3% higher when missing effectiveness was imputed, for the European and South American patients, respectively; only the 12.3% increment reached statistical significance. The probability for the linezolid group having both lower cost and superior effectiveness was 65.3% and 86.9% when missing effectiveness was scored as failures, or 75.2% and 80.7% when missing effectiveness was imputed, for the European and South American patients, respectively. CONCLUSIONS: The results suggest that linezolid is likely to represent good value for money compared to teicoplanin for the treatment of serious gram-positive infections.