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Background and Objective: Previous studies have shown efficacy of early introduction of peanut to prevent peanut allergy. It is currently unknown which diagnostic pathway is optimal after parental-reported reactions to peanut at home after early introduction., Methods: The PeanutNL cohort study included high-risk infants who were referred for early introduction of peanut. A subgroup of 186 infants with reactions to peanut at home underwent peanut skin prick tests and a supervised open oral food challenge (OFC) at a median age of 8 months. After a negative OFC, peanut was introduced at home., Results: Sensitization to peanut was detected in 69% of 186 infants, of whom 80% had >4 mm wheals in skin prick tests. An OFC with a cumulative dose of 4.4 g of peanut protein was performed in 163 infants with Sampson severity score grade I-III reactions at home; 120 challenges were negative. Peanut was subsequently introduced at home in infants with a negative challenge outcome. After 6 months, 96% were still eating peanut and 81% ate single portions of 3.0 g of peanut protein. One patient was considered to be peanut allergic after reintroduction of peanut at home., Conclusions: These data show that 65% of infants with reported reactions to peanut at home have negative OFCs. In those children, peanut could be introduced safely, and 96% were able to consume peanut regularly without reactions. Challenging infants younger than 12 months prevents the misdiagnosis of peanut allergy and enables safe continued exposure to peanut and the induction of long-term tolerance., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)