AimTo compare the safety and efficacy of intranasal high-dose dexmedetomidine (DEX) versus a combination of intranasal low-dose dexmedetomidine and oral chloral hydrate (DEX-CH) sedation during electroencephalography (EEG) in children. MethodsUnadjusted analysis, 1:1 propensity score matching (PSM), and inverse probability of treatment weighting (IPTW) were used to compare the sedation success rate, adverse effects, onset time, and recovery time of these two sedation methods for 6967 children who underwent EEG. ResultsA total of 6967 children were enrolled in this study, of whom 846 (12.1 %) underwent DEX intranasal sedation while 6121 (87.9 %) received DEX-CH sedation. No significant differences were observed in the sedation success rate with the first dose between the two groups [824 (97.4 %) for DEX vs. 5971 (97.6 %) for DEX-CH; RR 0.99; 95 % CI, 0.98–1.01; P = 0.79]. Similarly, there were no notable disparities in the incidence of adverse events [16 (1.9 %) for DEX vs. 101 (1.7 %) for DEX-CH; RR 1.15; 95 % CI, 0.68–1.93; P = 0.32]. However, intranasal DEX sedation compared with DEX-CH sedation was associated with lower vomiting [0 vs. 95(1.6 %); RR 0.04; 95 % CI, 0.02–0.6; P = 0.02] or more bradycardia [13(1.5 %) vs. 2(0.03 %); RR 47.03; 95 % CI, 10.63–208.04; P < 0.001]. Multivariate analysis using PSM and IPTW analysis yielded similar results. ConclusionBoth methods for EEG had high sedation success rate and low incidence of adverse events. High-dose intranasal DEX was more likely to induce bradycardia and had a shorter recovery time than the DEX-CH sedation, which was more likely to induce vomiting.