Burn injury induces a hypercatabolic inflammatory state, predisposing burn patients to malnutrition, poor wound healing, and infectious complications. We conducted this study to determine what effect a diet fortified with fish oil and arginine (FAD) would have on wound healing in a thermally injured population. Twenty-three thermally injured patients were enrolled in this randomized double blind enteral feeding study from July 2002 to August 2004. All study patients received isonitrogenous enteral intragastric feeding within 48 hours of admission. Patients were randomized to our standard diet (STD, ProBalance with Promix, Probalance from Nestlé, Glendale, CA; ProMix R.D., Navaco Laboratories, Phoenix, AZ) or a diet fortified with fish oil and arginine (FAD, Crucial, Nestlé Nutrition Glendale, CA) Diets were advanced as tolerated to meet 100% of estimated needs. The primary endpoint of the study was time to heal the first donor site. There were no statistical differences between the study groups with respect to baseline characteristics. Both diets were well tolerated, and there were no differences in the daily total kilocalories or protein intake per kilogram between the two diet groups throughout the study. Although nonsignificant, the patients in the FAD group showed a slightly faster healing time than those in the STD group (10.8 +/- 2.7 days vs 12.3 +/- 5.2 days, respectively). This trend was further accelerated when those with body surface area burns less than 30% were examined (patients with body surface area burns <30% in the FAD healed in 9.0 +/- 1.7 vs corresponding patients in the standard group who healed in 12.2 +/- 6.2, P = .63). Patients in the FAD group trended to more infections and more adverse complications. The adverse complications were predominantly associated with inhalation injuries. The role of fortified enteral diets in the outcomes of thermally injured patients deserves further study. Such a future study should be conducted in a multicenter trial and involve inhalation injury stratification systems to accurately score and randomize patients for inhalation injury. Finally, the frequency and pattern of infections in patients receiving fortified enteral diets deserves further evaluation.