ObjectiveTo assess the cost-effectiveness of drotrecogin alfa (activated) therapy, which was recently shown to reduce mortality in severe sepsis.DesignEstimates of effectiveness and resource use were based on data collected prospectively as part of a multicenter international trial. Estimates of hospital costs were based on a subset of the patients treated in the United States (33% of all enrolled patients). Lifetime projections were modeled from published sources and tested in sensitivity analyses. Analyses were conducted from the United States societal perspective, limited to healthcare costs, and using a 3% annual discount rate.SettingA total of 164 medical institutions in 11 countries.PatientsAdults ≥18 yrs of age with severe sepsis.InterventionsEligible patients were randomly assigned to receive a 96-hr intravenous infusion of drotrecogin alfa (acti-vated) at 24 &mgr;g/kg/hr (n = 850) or placebo (n = 840).Measurements and Main ResultsBase Case: incremental short-term (days 1–28) healthcare costs per day-28 survivor; Panel on Cost-Effectiveness in Health and Medicine Reference Case: incremental lifetime healthcare costs per quality-adjusted life-year. Over the first 28 days (short-term Base Case), drotrecogin alfa (activated) increased the costs of care by $9,800 and survival by 0.061 lives saved per treated patient. Thus, drotrecogin alfa (activated) cost $160,000 per life saved (with 84.7% probability that ratio is <$250,000 per life saved). Projected to lifetime (lifetime Reference Case), drotrecogin alfa (activated) increased the costs of care by $16,000 and quality-adjusted survival by 0.33 quality-adjusted life-years per treated patient. Thus, drotrecogin alfa (activated) cost $48,800 per quality-adjusted life-year (with 82% probability that ratio is <$100,000 per quality-adjusted life-year). Estimates were generally robust to sensitivity analyses, although cost-effectiveness deteriorated to >$100,000 per quality-adjusted life-year if survivors lived <4.6 yrs on average. Drotrecogin alfa (activated) cost $27,400 per quality-adjusted life-year when limited to patients with an Acute Physiology and Chronic Health Evaluation II score ≥25 and was cost-ineffective when limited to patients with a score <25.ConclusionsDrotrecogin alfa has a cost-effectiveness profile similar to that of many well-accepted healthcare strategies and below commonly quoted thresholds.