During a 1-year period, the authors examined clinical experience with drotrecogin alfa, activated for sepsis in a 24-bed medical-surgical intensive care unit. Drotrecogin alfa, activated was administered 46 times to 44 patients (3% of all intensive care unit admissions). Eighty-six percent of patients were on vasopressors; 95% were mechanically ventilated. Mean Acute Physiology and Chronic Health Evaluation II score was 22.0 at admission and 21.9 during the 24 hours before drug administration. The 28-day all-cause mortality was 36.4% and hospital mortality was 43.2%, trending higher (P = .10) than in the PROWESS study, which can be attributed to clinical use in patients who would not have met PROWESS study inclusion criteria. Failure to complete a 96-hour infusion of drotrecogin alfa, activated and transfer from another hospital or nursing home before treatment were associated with poor outcome. Total cost of hospital care, including mean drotrecogin alfa, activated drug cost of 7,312 US dollars, exceeded reimbursement by a mean of 18,227 US dollars.