Children with autism often need sedation for diagnostic procedures and they are often difficult to sedate. This prospective randomized double-blind control trial evaluates the efficacy and safety using intranasal dexmedetomidine with and without buccal midazolam for sedation in children with autism undergoing computerized tomography and/or auditory brainstem response test. The primary outcome is the proportion of children attaining satisfactory sedation. One hundred and thirty-six children received intranasal dexmedetomidine and 139 received intranasal dexmedetomidine with buccal midazolam for sedation. Combination of intranasal dexmedetomidine and buccal midazolam was associated with higher sedation success when compared to intranasal dexmedetomidine. Since intranasal and buccal sedatives required little cooperation this could be especially useful technique for children with autism or other behavioral conditions.