This trial was designed to test the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with refractory epilepsy. Pre-trial：144 patients were randomly assigned to ta-VNS group (n=98) or transcutaneous auricular non-vagus nerve stimulation (tn-VNS) control group (n=46). Treatment was conducted twice per day for 24 weeks. After 8, 16 and 24 weeks of treatment，the patients were evaluated according to the Modified Engel Scale (four classes). After 8 weeks，according to the medical ethic design, patients in tn-VNS group were switched into ta-VNS group uniquely. After 8 weeks’ treatment 41.0% and 27.5% of patients from ta-VNS and tn-VNS groups, respectively, experienced reduction in seizure frequency that reached I, II and III levels according to the standards of the Modified Engel Scale compared with the baselines, indicating significant difference in seizure reduction between the two groups. After 24 weeks of treatment, ta-VNS patients had a 47.7% reduction, and tn-VNS, with an additional 16 weeks of treatment, reached 47.5% in reduction. After 8 weeks’ treatment, the percentages of average seizure frequency in ta-VNS and tn-VNS were reduced by 42.6% and 11.5% respectively, providing a statistically significant difference in the results between the two groups (P<0.05). In addition, there were significant improvements in electroencephalograph (EEG) and the quality of daily life of the patients after treatment. The results show that this ta-VNS treatment can effectively reduce the frequency of seizures and improve the patient's quality of life. This may be an effective treatment for refractory epilepsy. At the same time，it is also safe，economic, and widely applicable.