Objective A small sample exploratory study was carried out to verify the effectiveness and safety of vagal nerve stimulation （VNS） intervention in patients with treatment-resistant depression （TRD）. Methods From February 2018 to December 2020， five TRD patients who met the inclusion and exclusion criteria were screened and included in the outpatient department of Beijing Anding Hospital for VNS. The efficacy and safety were evaluated at 2 weeks after operation （startup commissioning parameters） and 1， 6 and 12 months after startup. The depressive symptoms of patients were evaluated by 17 item Hamilton Depression Scale to evaluate the curative effect， and the complications and adverse reactions were observed. Results The symptoms of 5 patients began to improve about 1 month after operation. 6 months after the start of treatment， 4 patients achieved effective treatment （HAMD-17 reduction rate ≥ 50%）， and 2 patients achieved clinical remission （HAMD-17 ≤ 7）. None of the 5 patients had surgery related or material related complications. Hoarseness， shortness of breath and foreign body sensation in the throat were transient. Conclusions This study preliminarily explored the effect of VNS in the treatment of TRD in the domestic population. Four patients achieved effective treatment 6 months after the start of treatment， and there were no serious adverse events.