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We report the 3\u2010year outcomes of a multicenter, prospective pilot study of RS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RS was randomized to 20 or 24Gy targeting the amygdala, hippocampus, and parahippocampal gyrus. Seizure diaries evaluated the final seizure remission between months 24 and 36. Verbal memory was evaluated at baseline and 24m with the Wechsler Memory Scale\u2013Revised (WMS\u2010R) and California Verbal Learning Test (CVLT). Patients were classified as having \u201csignificant improvement,\u201d \u201cno change,\u201d and \u201csignificant impairment\u201d based on relative change indices.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirteen high\u2010dose and 17 low\u2010dose patients were treated. Both groups showed significant reductions in seizures by 1 year after treatment. At the 36\u2010month follow\u2010up evaluation, 67% of patients were free of seizures for the prior 12 months (high dose: 10\/13, 76.9%; low dose: 10\/17, 58.8%). Use of steroids, headaches, and visual field defects did not differ by dose or seizure remission. The prevalence of verbal memory impairment was 15% (4\/26 patients); none declined on more than one measure. The prevalence of significant verbal memory improvements was 12% (3\/26).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>RS for unilateral mesial temporal lobe epilepsy offers seizure remission rates comparable with those reported previously for open surgery. There were no major safety concerns with high\u2010dose RS compared with low\u2010dose RS. Additional research is required to determine whether RS may be a treatment option for some patients with mesial temporal lobe epilepsy. 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