BackgroundDental procedures under general anesthesia (DGA) was found to improve the oral health-related quality of children’s life. However, some parents and pediatricians expressed concern about the neurotoxicity of general anesthesia. The purpose of this trial was to whether DGA in children has an adverse effect on neurocognition.MethodsIn this prospective, assessor-masked, controlled, equivalence trial, we recruited 340 children younger than 7 years who were undergoing caries treatment between Feb 1, 2019, and Aug 31, 2019, without factors affecting neurodevelopment. They received either sevoflurane-based general anesthesia or awake-local anesthesia. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition was used to evaluate the neurocognitive function of children at 6 months after surgery, and the Full-Scale IQ (FSIQ) was selected as the primary outcome. The predefined clinical equivalence margin was 5 (1/3 SD of FSIQ score). If the 95% CI of the difference between the average FSIQ score of the two groups is within − 5 to + 5, then the two groups are equivalent.ResultsThe outcome data were obtained from 129 children in the general anesthesia group and 144 in the local anesthesia group. The median length of general anesthesia was 130 min (IQR 110–160). The mean FSIQ score in the general anesthesia group was 103·12 (SD 8.94), and the mean of the local anesthesia group was 103·58 (SD 8.40). There was equivalence in means of FSIQ score between the two groups (local minus general anesthesia 0.46, 95% CI − 2.35 to 1.61). There was no significant difference in FSIQ scores between different age groups and different anesthesia durations. Only the mother’s education could affect the primary outcome.ConclusionsIn this trial, prolonged DGA with a sevoflurane-only anesthetic in preschool children, does not adversely affect neurocognitive function at 6 months after surgery compared with awake-local anesthesia.Trial registrationChinese Clinical Trial Registry, ChiCTR1800015216. Registered Mar 15 2018.