Background: The role of partially hydrolyzed formulas (pHF) as a nutritional intervention for the prevention of Allergic Manifestations (AM) remains debatable, and the effectiveness of each specific pHF should be longitudinally examined. Objective: To investigate whether the risk-reduction effect of a specific pHF compared to a standard formula (SF) on Atopic Dermatitis (AD) within the first 6 months of life observed in the Allergy Reduction Trial (A.R.T.) persists at the age of 5 years and, if it applies to other AM. Methods: Parents/legal guardians of the A.R.T. participants who constituted the Intention-to-Treat population set (N=551) were invited to answer an enriched validated questionnaire regarding doctor diagnosis of AM between 1-5 years of age, including AD, Food Allergy (FA), Asthma, and Allergic Rhinitis. Results: Four hundred and fifty-five subjects (83%) completed the 5-year follow-up (pHF: 131/160, SF: 145/171 and EBF: 179/220). Infant feeding with the pHF resulted in 87% risk-reduction of FA [1,5% vs 12.4%, RR 0.13 (0.03-0.58), p=0.007] between the ages of 1-5 years compared to SF. The RR from birth to 5 years was significantly lower in the pHF group, for the development of any AM [32.7% vs 51.7%, RR 0.73 (0.57-0.94), p=0.02], AD [22.1% vs 38.5%, RR 0.58 (0.41-0.83), p=0.003] and, FA [10.5% vs 20.4%, RR 0.53 (0.29-0.95), p=0.03] compared to the SF group. Conclusion: In non-exclusively breastfed infants at high-risk for allergy, mixed-feeding with a specific whey-based pHF may reduce the risk of atopic dermatitis and food allergy from birth up to the age of 5 years.