Background: There is a paucity of data evaluating the efficacy of nutrition support in traumatic brain-injured patients induced into barbiturate coma for refractory intracranial hypertension. Our objective was to evaluate the efficacy of enteral nutrition in a select group of trauma patients. Methods: Prospective data were collected on severe traumatic brain-injured patients over a 4-year period. Patients were stratified by whether or not they were induced into a barbiturate coma. Barbiturate coma was defined as per American Association of Neurological Surgeons (AANS) guidelines. All patients were initially fed via the enteral route via a nasogastric feeding tube. Patients who did not tolerate feedings within 48 hours started receiving prokinetic agents. Feeding tolerance was defined as ability to tolerate enteral feedings with <150 mL of gastric residuals every 6 hours for >72 hours. Results: Fifty-seven patients were induced into a barbiturate coma. All were victims of bluntforce trauma. Forty-two of 57 (74%) patients were men, with a mean age of 37 ± 12 years and a mean injury severity score of 24 ± 10. Thirty-eight of the 57 (67%) patients had an isolated traumatic brain injury. All 57 patients failed enteral nutrition via the nasogastric route after the first 48 hours of nutrition initiation after barbiturate coma was fully achieved by protocol criteria. Prokinetic agents demonstrated no improvement in feeding tolerance after the subsequent 48-72 hours. Of the 12 patients who had a postpyloric feeding tube placed, only 25% tolerated enteral nutrition for >48 hours. Conclusions: Patients with traumatic brain injury induced into barbiturate coma develop a significant ileus that is refractory to prokinetic agents. Only a marginal improvement is seen when the postpyloric route is obtained. Early parenteral nutrition should be considered in this patient population.