This prospective study describes the current prognosis of patients in acute Organ System Failure (OSF). Objective definitions were developed for five OSFs, and then 5677 ICU admissions from 13 hospitals were monitored. The number and duration of OSF were linked to outcome at hospital discharge for each of the 2719 ICU patients (48%) who developed OSF. For all medical and most surgical admissions, a single OSF lasting more than 1 day resulted in a mortality rate approaching 40%. Among both medical and surgical patients, two OSFs for more than 1 day increased death rates to 60%. Advanced chronologic age increased both the probability of developing OSF and the probability of death once OSF occurred. Mortality for 99 patients with three or more OSFs persisting after 3 days was 98%. The two patients who survived were both young, in prior excellent health, and had severe but limited primary diseases. These results emphasize the high death rates associated with acute OSF and the rapidity with which mortality increases over time. The prognostic estimates provide reference data for physicians treating similar patients.