Introduction Failure to secure an airway during general anesthesia is a major cause of adverse events (AEs) in children. The safety of peddiatric anesthesia may be improved by identifying the incidence of AEs and their attributed risk factors. However, previous large cohort studies have not been appropriately designed to explore such aspects. Thus, this study aims to deternine the incidence of AEs and the risk factors attributed to airway management under general anesthesia in children. Methods and design This prospective, multi-center, registry-based, observational study will be conducted in four tertiary care hospitals in Japan from June 2022 to May 2025. Children younger than 18 years of age undergoing surgical and/or diagnostic test procedures under general anesthesia or sedation by anesthesiologists will be enrolled in this study. Data on patient characteristics, discipline of anesthesia providers, and methodology of airway management will be collected through a standardized verification system under monitoring by institutional research leaders among the recruited institutions to minimize the loss of collected data. The primary outcome and exposure are AEs and presence of difficult airway features with potential confounders, which are related to the failure to secure the airway, and the variability in the anesthesia providers’ levels, adjusted using hierarchical multivariable regression models with mixed effects. Discussion This study will determine the incidence of AEs and the risk factors related to airway management under general anesthesia in children. Trial registration This study is registered as a prospective observational study in the University hospital Medical Information Network (UMIN) (registration number UMIN000047351, April 1, 2022).