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Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System.This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis.Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction90%). For the super responders, two of the four patients had the device implanted for2 years. The response rate was 70% for those in whom the device was implanted for2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported.Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD-DRE.