In order to define the role of intracranial and extracranial complications in determining outcome from severe head injury, 734 patients from the Traumatic Coma Data Bank were analyzed. Nine classes of intracranial and 13 classes of extracranial complications occurring within the first 14 days after admission were analyzed, while controlling for age, admission Glasgow Coma Scale motor score, early hypoxia or hypotension, and severe extracranial trauma. Outcome for survivors was based on the last recorded Glasgow Outcome Scale score, obtained a median of 521 days after injury. Intracranial complications did not significantly alter outcome for the study group. Of the extracranial complications, pulmonary, cardiovascular, coagulation, and electrolyte disorders occurred most frequently at 2 to 4 days. Infections developed later, peaking at 5 to 11 days. Gastrointestinal, renal, and hepatic complications followed no specific time course. Electrolyte abnormalities were the most frequent occurrence (59% of patients) but did not alter outcome. Pulmonary infections (41%), shock (29%, systemic blood pressure < or = 90 mm Hg for 30 minutes or more), coagulopathy (19%), and septicemia (10%) were significant independent predictors of an unfavorable outcome. Backward-elimination, stepwise logistic regression modeling indicated that the estimated reduction of unfavorable outcome was 2.9% for the elimination of pneumonia, 3.1% for coagulation disturbances, 1.5% for septicemia, and 9.3% for shock. These data suggest that extracranial complications are highly influential in determining the outcome from severe head injury and that significant improvements in outcome in a sizeable proportion of patients could be accomplished by improving the ability to prevent or reverse pneumonia, hypotension, coagulopathy, and sepsis.