Thirty-seven ventilator-dependent blunt trauma patients (ISS 36±15) were randomized at 24 hours after injury to receive parenteral (TPN) (n = 15), enteral (TEN) (n = 12), or parenteral plus enteral (PN/EN) (n = 10) nutrition. The TEN and PN/EN patients had endoscopically placed transpyloric feeding tubes. Patients who had nutritional complications were two TPN (13%), three TEN (25%), and five PN/EN (50%). Enteral complications were tube occlusion (two), failed duodenal intubation (one), patient extubation of feeding tube (one), gastric reflux (two), and abdominal distention (two). Mortality rates were not different between the groups, but were significantly related to the nutrition-associated complications (p = 0.01): four deaths in ten (40%) with complications and one death in 27 (3.7%) without complications. All four deaths associated with complications occurred in the four with gastric reflux or abdominal distention. No deaths occurred in the other 18 TEN or PN/EN patients (p = 0.0001). Of the four deaths, three were associated with ARDS and respiratory infection (75%). Conclusions: In mechanically ventilated blunt trauma patients, endoscopic transpyloric tube placement and feeding has a substantial failure rate (36%). Intolerance to duodenal feeding has a remarkably high mortality (100%) in patients in whom gut dysfunction may be a manifestation of injury severity or directly affect survival.