Children with autism and autism spectrum disorders have a high incidence of neurologic comorbidities. Consequently, evaluation with magnetic resonance imaging (MRI) is deemed necessary. Sedating these patients poses several challenges. This retrospective study compared the efficacy and safety of dexmedetomidine to propofol in sedating autistic patients undergoing MRI. There were 56 patients in the dexmedetomidine group and 49 in the propofol group. All of the patients successfully completed the procedure. Recovery and discharge times were significantly lower in the propofol group, while the dexmedetomidine group maintained more stable hemodynamics. Both propofol and dexmedetomidine proved to be adequate and safe medications in the sedation of autistic children undergoing MRI.