Vagus nerve stimulation (VNS) has been increasingly studied in treating treatment-resistant depression (TRD), but the findings have been mixed. This updated meta-analysis was conducted to examine the efficacy and safety of adjunctive VNS for TRD. Controlled studies reporting on the efficacy and safety of adjunctive VNS for TRD were screened, identified and analyzed. Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were analyzed using RevMan version 5.3. Three controlled studies with a total of 1048 patients with TRD compared VNS (n = 622) with control (n = 426) groups. Only one study was rated as 'high quality' using the Jadad scale. Adjunctive VNS was significantly superior to the control group regarding study-defined response [SMD:1.96 (95%CI:1.60, 2.40), P < 0.00001, I2 = 0%]. Patient-reported voice alteration occurred more frequently with adjunctive VNS for patients with TRD. No significant group differences were found regarding discontinuation due to any reason [RR:0.50 (95%CI:0.12, 2.09), P = 0.34, I2 = 85%]. Adjunctive VNS appeared to be effective and relatively safe treatment for TRD. Further randomized controlled trials are needed to confirm the efficacy and safety of VNS for TRD.