ObjectiveTo assess morbidity in patients with severe sepsis managed with and without drotrecogin alfa (activated).DesignAnalysis of secondary end points in a prospective, randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (PROWESS).SettingA total of 164 medical institutions in 11 countries.PatientsA total of 1,690 consecutive adult patients with severe sepsis.InterventionsA 96-hr infusion of drotrecogin alfa (activated) (human recombinant activated protein C) or placebo.Measurements and Main ResultsSequential Organ Failure Assessment (SOFA) scores for cardiovascular, respiratory, renal, hematologic, and hepatic organ systems were measured for 28 days. Mean cardiovascular SOFA scores were significantly lower for patients treated with drotrecogin alfa (activated) compared with placebo patients over this time period (p= .022). Drotrecogin alfa (activated)–treated patients also showed significantly faster resolution of cardiovascular (p= .009) and respiratory (p= .009) dysfunction and significantly slower onset of hematologic organ dysfunction (p= .041) compared with placebo patients for days 1 to 7. No significant differences in morbidity were observed between treatment groups among 28-day survivors.ConclusionDrotrecogin alfa (activated) demonstrated significant improvements in organ function compared with placebo in a large phase 3 clinical trial that has shown a mortality benefit in patients with severe sepsis.