Context: Previous studies demonstrated that vagus nerve stimulation (VNS) is an effective therapy for refractory epilepsy.Objective: The present study was designed to examine whether transcutaneous auricular vagus nerve stimulation (ta-VNS) is an effective approach for patients with refractory seizures.Design, Setting, and patients: A pilot study was conducted first on 50 patients with refractory seizures to preliminarily observe the therapeutic effect of ta-VNS.Then, a randomized controlled trial (RCT) was conducted on other 144 epilepsy patients who were randomly assigned to the ta-VNS group (n=98), and the non-transcutaneous auricular vagus nerve stimulation (tn-VNS) control group (n=46).The treatment was performed twice a day for 24 weeks.Patients who were neither in the ta-VNS group nor in the tn-VNS group accepted medication at the same time.Intervention: Transcutaneous Electrical Nerve Stimulation and the double blind method were used in the present study.The results were not disclosed till the end of the 24 weeks treatment.Main Outcome Measure: The seizure frequency and severity were assessed in week 8, 16 and 24 of the treatment according to the modified Engel scale.The outcomes were divided to four classes.Results: In the pilot study, of the 50 epilepsy patients, after 8 weeks treatment, 6 were seizure free and 12 had a 50-89% reduction in seizure frequency;after 24 weeks treatment 8 were seizure free and 9 had a 50-89% reduction in seizure frequency.In the RCT study, of the 98 patients in the taVNS group, after 8 weeks treatment, 10 were seizure free and 25 had a 50-89% reduction in seizure frequency;after 24 weeks treatment 15 were seizure free;26 had a 50-89% reduction and 6 had a ≥ 90% reduction in seizure frequency.In the tn-VNS control group, of the 46 patients, only 3 were seizure free, and 11 had a 50% reduction in seizure frequency after the first 8 weeks treatment.Interestingly, after an additional 16-week treatment of taVNS, of the 46 patients, 5 were seizure free, 1 had a ≥ 90% reduction and 15 had a 50-89% reduction in seizure frequency respectively.The differences in seizure frequency reduction among groups were significant (P < 0.05).Conclusions: Similar to the therapeutic effect ofVNS, ta-VNS can suppress epileptic seizures as a safe, effective,economic and widely applicable treatment option for refractory epilepsy.