Background <p>Observational studies indicate that higher protein intake can promote long-term growth and reduce the risk of neurodevelopmental impairment (NDI) in extremely preterm infants fed human milk.</p> Methods <p>This was a secondary analysis of a randomized trial in which 56 preterm infants born at 25–28 weeks of gestation were randomly assigned to receive either standard fortified milk or fortified milk supplemented with extensively hydrolyzed protein after postnatal day 14. The primary outcome of this analysis was moderate to severe NDI or death at approximately 2 years of corrected age. Anthropometric outcomes at 2 years of corrected age were also analyzed.</p> Results <p>The outcome of moderate to severe NDI or death was assessed in 52 infants and did not differ between groups (42% vs. 43%). Bayley assessments were completed in 33 eligible infants (61%). Cognitive, language, and motor scores did not differ between groups. Similarly, weight (<i>n</i> = 35), length (<i>n</i> = 30), head circumference (<i>n</i> = 28) and their respective z-scores at approximately 2 years of corrected age did not differ between groups.</p> Conclusion <p>In this analysis with lower-than-expected follow-up rates, a protein-enriched fortified milk diet neither reduced the risk of moderate to severe NDI nor promoted long-term growth.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Protein-enriched fortified milk diets after the first 2 postnatal weeks do not appear to significantly affect long-term growth or the likelihood of surviving without neurodevelopmental impairment in infants born extremely preterm.</p> </ItemContent> <ItemContent> <p>Further research is needed to determine the optimal timing for introducing protein-enriched fortified milk diets.</p> </ItemContent> <ItemContent> <p>More randomized clinical trials with extended follow-up data are essential to provide evidence-based guidance for clinical practice.</p> <p><b>Category of Study</b>: Clinical</p> </ItemContent> </UnorderedList></p>