Background: Respiratory tract infection in infancy can cause symptomatic wheezing or asthma later in childhood. Eosinophil-derived neurotoxin (EDN), a single-chain polypeptide with a molecular mass of 18.6 kDa, has been proposed to play a role in the development of recurrent wheezing and asthma; however, this fact remains unclear. Therefore, this study aimed to determine whether EDN is a risk factor for recurrent wheezing and asthma in pediatric patients following respiratory tract infection. Method: From October 2021 to March 2022, we tracked children hospitalized for respiratory tract infections at the Chengdu Women’s and Children’s Central Hospital. All patients underwent medical history collection, EDN testing, and induced sputum testing and were followed up at 6 months and 1 year post-discharge. Multifactor analysis was subsequently conducted using stepwise logistic regression analysis. Results: A total of 183 participants were enrolled in this study. Statistical analyses revealed that elevated EDN levels increased the risk of asthma following respiratory infection in young children. Children with a history of allergies or allergic rhinitis further exhibited elevated EDN levels. Conclusion: EDN may be a useful biomarker to predict the development of asthma following respiratory tract infections in infants and could be used as a useful screening tool for allergic diseases, particularly allergic rhinitis.