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<p><strong>Objective</strong> To study the efficacy and possible mechanism of deep brain stimulation (DBS) in bilateral anterior thalamic nuclei (ATN) for drug-resistant epilepsy.<strong> Methods</strong> Three cases with drug-resistant epilepsy underwent DBS in bilateral ATN. Preoperative and postoperative assessment included the frequency of seizures, seizure types, kinds and dosage of anti-epileptic drugs (AEDs), and imaging and EEG examination. <strong>Results</strong> Case 1 was followed up for 28 months, with only one seizure attack occurred due to missing doses. Video EEG (VEEG) during the follow-up period showed that a single unilateral spike-slow wave discharge was found by accident in one year after DBS. As for Case 2, intermittent time was significantly prolonged during the follow-up of 24 months. VEEG during the follow-up period showed interictal right frontal-central-parietal slow wave. Case 3 was followed up for 3 months, and VEEG examination during the follow-up period revealed decrease of diffuse spike-slow wave, while bilateral occipital spike-slow wave could be seen in interictal phase. Without any change of type and dose in taking AEDs after DBS, seizure frequency was reduced by 100% in Case 1, 25% in Case 2, and almost 55% in Case 3. <strong>Conclusions </strong>DBS therapy is an effective treatment for drug-resistant epilepsy. It could significantly reduce the frequency of attacks, or even completely control the attack, and improve the patients' quality of life.</p><p> </p><p><strong>DOI: </strong>10.3969/j.issn.1672-6731.2015.09.007</p>