OBJECTIVES: In the PROWESS trial (n=1690), drotrecogin alfa (activated) (recombinant human Activated Protein C) significantly decreased the 28-day mortality in adults with severe sepsis compared with placebo (ARR 6,1%; p=0,005). A cost-effectiveness analytical model was conducted to assess the efficiency of the drug in Spain in the trial population and in the expected approved indication (patients with multiple organ failures). METHODS: National Health Service perspective was used in the analysis. Effectiveness and resource use were obtained from data collected prospectively in the trial. Spanish costs data of patients treated in intensive care were applied. Direct costs assessed were drug cost, costs up to 28 days, and to final discharge. Life expectancy was estimated using actual age and sex, and Spanish life tables, and an adjustment for post discharge mortality associated with severe sepsis. Cost per hospital survivor and incremental hospital cost per life year gained (LYG) were calculated. LYG were not discounted in the base case analysis. Sensitivity analysis was applied adjusting for patterns of care, ICU costs, comorbidity and discount rate. RESULTS: In patients with multiple organ failure, drotrecogin alfa (activated) saved 7.3 additional lives in hospital per 100 treated patients at 28 days when compared with placebo (p <0,05) (NNT=14). The cost per hospital survivor was €119,857. Hospital survivors were estimated to live 12.2 years. The cost-effectiveness of drotrecogin alfa (activated) was €9,799 per LYG when compared with placebo (€13,594 per LYG for the trial population). The sensitivity analysis indicated that the largest influence on costs were the assumptions of the discount and reduction in life expectancy of patients. CONCLUSIONS: In Spain, drotrecogin alfa (activated) has shown to be efficient in the treatment of severe sepsis. The incremental CE is better than many well-accepted and common healthcare interventions.