Objective:To determine the effect of early enhanced enteral nutrition (EN) on clinical outcome of head-injured patients.Design:Prospective, randomized, controlled trial.Setting:Tertiary neurosurgical and trauma center.Patients:Eighty-two patients suffering head injury and requiring mechanical ventilation.Interventions:Patients were randomized to receive standard EN (gradually increased from 15 mL/hr up to estimated energy and nitrogen requirements) or enhanced EN (started at a feeding rate that met estimated energy and nitrogen requirements) from day 1. Good neurologic outcome (Glasgow Outcome Scale score of 4 or 5) was determined at 3 and 6 months after injury, and the incidence of infective and total complications was determined during the hospital stay up to 6 months.Measurements and Main Results:Disease severity assessed by best preintubation Glasgow Coma Scale score, pupillary responses, Injury Severity Score, Acute Physiology and Chronic Health Evaluation II score, computed tomographic scan categorization, and age was similar in both groups. Intervention patients had a higher percentage of energy (p= .0008) and nitrogen (p< .0001) requirements met by EN in the first week after injury. Neurologic outcome at 6 months was similar between groups, but there was a tendency for more intervention patients to have a good neurologic outcome at 3 months than control patients (61% vs. 39%,p= .08). Fewer intervention patients had an infective complication (61% vs. 85%,p= .02) or more than one total complication (37% vs. 61%,p= .046) compared with control patients. Enhanced EN was associated with a reduction in the ratio of serum concentration of C-reactive protein to albumin up to day 6 after injury (p= .004).Conclusions:Enhanced EN appears to accelerate neurologic recovery and reduces both the incidence of major complications and postinjury inflammatory responses.