Objective The purpose of this study is to evaluate the efficacy and safety of sedation of oral chloral hydrate combination with intranasal dexmedetomidine for magnetic resonance imaging (MRI) in pediatric patients. Methods In a prospective single-blinded randomized clinical trial, a total 247children were randomly assigned to received oral chloral hydrate of 50mg/kg combination with different intranasal dexmedetomidine doses of 2.0 g/kg (group A), 1.5 g/kg (group B) and 1.0 g/kg (group C), respectively. The efficacy and safety of sedative regimens were evaluated based on the sedation onset time, wake-up time, total sedation time and clinical side-effects. A stratified analysis was used to explore the effects of f age and developmental status on the success rate of sedation in pediatric patients. Results The total success rate of sedation for MRI was 89.1%. The success rate of sedation, the sedation onset time and the incidence of side-effects had no significantly difference among groups (P > 0.05). However, the wake-up time and total sedation time in group C was shorter significantly compared with group A and group B (P < 0.05). Age and developmental status were not independent factors of the success rate of sedation. Conclusions Oral chloral hydrate combined with intranasal dexmedetomidine could be used effectively and safely for pediatric sedation in MRI. A dosage of intranasal dexmedetomidine 1g/kg and oral chloral hydrate 50mg/kg was appropriate for routine sedation of MRI scan in pediatric patients.