Background:We hypothesized that enteral protein supplementation in infants with brain injury would be safe and well tolerated and improve growth. Materials and Methods: Twenty-five infants with perinatal brain injury were randomized to a high-protein (4 g/kg/d) or standard-protein diet and followed for 12 months. Results: The whey protein powder was well tolerated by 9 of the 13 infants in the high-protein group, and no adverse events related to the supplement were seen. The protein group had higher serum urea nitrogen at 10 and 30 days after study initiation but no difference in bicarbonate levels at either time point. Infants in the protein group maintained their weight z score from birth to 3 months of age, while infants in the standard group had a significant decrease in their weight z score over the same time period. Conclusion: These results suggest that enteral protein supplementation may reduce growth failure in infants with brain injury.