A prospective cohort analysis of adult medical-surgical patients from a nationally representative sample of 40 U.S. hospitals. 15,973 consecutive, nontraumatic ICU admissions and a comparison group of 687 head trauma admissions. None. Patients' gender, age, treatment location before ICU admission, comorbidities, admission diagnosis, daily physiologic measurements, Glasgow Coma Scale score, Acute Physiology and Chronic Health Evaluation (APACHE IIITM) score, subsequent hospital mortality rate, and unit-specific sedation practices were noted. Hospital mortality rates were stratified by the first ICU day Glasgow Coma Scale score for all admissions. The relationship between the Glasgow Coma Scale score and outcome for two high mortality medical diagnoses (post-cardiac arrest and sepsis) were also examined and compared to the relationship found in patients with head trauma. The Glasgow Coma Scale score on ICU admission had a highly significant (r2 = .922, p < .0001) but nonlinear relationship with subsequent outcome in ICU patients without trauma. Discrimination of patients into high- or low-risk prognostic groups was good, but discrimination in the intermediate levels (Glasgow Coma Scale score of 7 to 11) was reduced. This relationship varied within the operative and nonoperative groups, and also within different disease categories, various age groups, and certain ranges of the Glasgow Coma Scale score. A reduced initial Glasgow Coma Scale score associated with sepsis was a combination of factors associated with a higher mortality rate than that found in patients with head trauma. The proportion of patients who could not be assigned a Glasgow Coma Scale score because of sedation/paralysis varied widely across ICUs. The overall predictive capability of the APACHE III Prognostic Scoring System was improved by incorporating the Glasgow Coma Scale score. We demonstrated the prognostic importance of admission levels of consciousness as measured by the Glasgow Coma Scale score on ICU and hospital mortality rates. We concluded that the Glasgow Coma Scale score may be used to stratify and predict mortality risk in general intensive care patients, but lack of sensitivity in the intermediate range of Glasgow Coma Scale Score should be noted. Ideally, the Glasgow Coma Scale score should also be applied in the context of other physiologic information and the patient's specific diagnosis. Variation in the use of sedatives in different ICUs means that imputing or substituting a value other thatn normal for an unobtainable Glasgow Coma Scale score may introduce a substantial treatment bias into subsequent outcome predictions. (Crit Care Med 1993; 21:1459–1465)