Early enteral nutrition may preserve gut function and prevent bacterial translocation after trauma. Standard enteral nutrition uses products which contain intact protein and require digestion for absorption. Peptide-based enteral nutritional products are better absorbed and stimulate the release of gut trophic hormones. This study was performed to determine whether a peptide-based (PEP) product (Reabilan HN) was better tolerated and/or produced better hepatic protein responses in patients after trauma when compared to an intact-protein (PRO) formula (Osmolite HN). Eighteen trauma patients were prospectively randomized to PEP (n = 9) or PRO (n = 9) enteral diets administered via nasoduodenal tubes (within 1-2 days of injury). Visceral protein synthesis was assessed by measuring baseline and 1 week pre-albumin and transferrin levels. Diarrhea was defined as greater than 300 gm/day of stool. Groups were similar in age, Injury Severity Score (ISS), caloric intake, and protein intake. Protein levels increased significantly faster in PEP patients despite similar urea nitrogen excretion. Diarrhea developed in four (44%) PRO patients and none of the PEP patients. Three of the PRO patients were switched to PEP after one week and diarrhea subsided in all three patients. Peptide-based enteral diets are associated with better hepatic protein responses and less diarrhea compared to intact-protein diets.