Stereotactic electroencephalography-guided three-dimensional radiofrequency thermocoagulation (SEEG-3D RFTC) is a minimally invasive treatment for medial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This study aimed to investigate the long-term prognosis after SEEG-3D RFTC treatment in patients with MTLE-HS.This single-center retrospective study included 28 patients with MTLE-HS treated with SEEG-3D RFTC from January 2016 to May 2018. Postoperative curative effects were evaluated using the Engel classification, and the patients were followed up for 5 years.The proportions of patients categorized as Engel I between one and five years after surgery were 72.41% (12 months after surgery), 67.86% (18 months after surgery), 62.07% (24 months after surgery), 50.00% (36 months after surgery), 42.86% (48 months after surgery), and 42.86% (60 months after surgery), respectively. Regarding long-term efficacy, based on the Engel classification, SEEG-3D RFTC showed room for improvement.This was the first study to evaluate the efficacy of SEEG-3D RFTC for MTLE-HS with long-term follow-up. SEEG-3D RFTC is a promising alternative for patients with MTLE-HS.This article is protected by copyright. All rights reserved.