OBJECTIVES: The PROWESS study (N=1690) demonstrated that drotrecogin alfa (activated) significantly reduced 28-day mortality when added to conventional therapy in the treatment of severe sepsis. The aim of the current study was to generate and compare estimates of cost-effectiveness of drotrecogin alfa (activated) in three European counties: Germany (GM), Austria (AS) and Switzerland (CH). METHODS: We developed a core decision analytic model and performed cost-effectiveness calculations from the (national) health service payer's perspective. Local life-tables were applied to estimate long-term survival benefits from hospital trial mortality (ARR=6.1%). Trial resource use (ICU stay, duration of organ support, hospital stay, drotrecogin alfa [activated]) was valued using published country-specific costs. Cost-effectiveness was expressed as the incremental cost per life year gained (LYG). Analysis was repeated using the resource use patterns of European trial patients only (N=507); and using the resource use patterns from local non-trial data. Analysis was repeated for patients with a high risk of mortality (two or more organ dysfunction at baseline, ARR=7.3%) RESULTS: Cost effectiveness was estimated at €14,400 (GM) and €15,400 (AS) LYG (€22,400 and €24,700 discounting LYG at 3%) Restricting analysis to high risk patients produced better cost-effectiveness due to greater ARR: €10,400 (GM) and €11,300 (AS) (€13,500 and €15,100 discounting LYG at 3%). Estimates using European trial patients' resource use or country-specific resource use showed consistent cost-effectiveness. The results for Switzerland are also presented and compared. CONCLUSIONS: The cost effectiveness of drotrecogin alfa (activated) is driven by the drug cost and lives saved, which were assumed constant for each country. The trial showed only small increases in other resource use associated with increased numbers of survivors. Applying local life tables, unit costs, or patterns of care did not alter the conclusion that drotrecogin alfa (activated) is a cost effective treatment for severe sepsis.