OBJECTIVE: Transcutaneous auricular vagal nerve stimulation (tVNS) has been investigated as a potential non-invasive therapy in addition to standard medical care in patients with drug-resistant epilepsy (DRE). This meta-analysis evaluates the efficacy and safety of tVNS compared to sham stimulation in patients with DRE. METHODS: A systematic search was conducted in three electronic databases (PubMed, Scopus, Cochrane) to identify randomized controlled trials (RCTs) comparing tVNS versus sham stimulation for the treatment of DRE. The Cochrane risk of bias tool for randomized trials was utilized for quality assessment. RESULTS: Four RCTs, comprising 368 patients, with 232 patients in the tVNS group, were included. The meta-analysis revealed that tVNS significantly reduces seizure frequency, as expressed by mean monthly seizure number (mean difference [MD] -3.01, 95 % confidence interval [CI] [-5.37 to -0.65], p < 0.01, I = 0 %) and percentage seizure reduction (MD 17.57 %, 95 % CI [1.90 to 33.25], p = 0.03, I = 0 %) at the end of treatment. The analysis also indicated a potential effect on responder rate (odds ratio 2.00, 95 % CI [0.98 to 4.05], p = 0.06, I = 42 %), although not statistically significant. No significant differences between groups were found regarding seizure freedom, depression, and QOL. Adverse events reported were mostly mild and transient, with no significant differences between groups and comparable discontinuation rates. CONCLUSIONS: This meta-analysis supports the efficacy and safety of tVNS as an adjunctive therapy for the treatment of DRE. Due to significant methodological concerns in some of the included studies, well-designed RCTs are needed to investigate the efficacy of tVNS on seizure and non-seizure outcomes in patients with DRE.