This study explored the efficacy and safety of transcutaneous vagus nerve stimulation (t-VNS) in patients with pharmacoresistant epilepsy. A total of 60 patients were randomly divided into two groups based on the stimulation zone: the Ramsay-Hunt zone (treatment group) and the earlobe (control group). Before and after the 12-month treatment period, all patients completed the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Liverpool Seizure Severity Scale (LSSS), and the Quality of Life in Epilepsy Inventory (QOLIE-31). Seizure frequency was determined according to the patient's seizure diary. During our study, the antiepileptic drugs were maintained at a constant level in all subjects. After 12 months, the monthly seizure frequency was lower in the treatment group than in the control group (8.0 to 4.0; P-0.003). This reduction in seizure frequency was correlated with seizure frequency at baseline and duration of epilepsy (both P > 0.05). Additionally, all patients showed improved SAS, SDS, LSSS, and QOLIE-31 scores that were not correlated with a reduction in seizure frequency. The side effects in the treatment group were dizziness (1 case) and daytime drowsiness (3 cases), which could be relieved by reducing the stimulation intensity. In the control group, compared with baseline, there were no significant changes in seizure frequency (P = 0.397), SAS, SDS, LESS, or QOLIE-31. There were also no complications in this group. (C) 2014 Published by Elsevier Inc.