Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a widespread invasive procedure for treating drug‐resistant epilepsy. Nonetheless, there is a persistent debate regarding the short‐term and long‐term efficacy and safety of ANT‐DBS. Thus we conducted a systematic review and meta‐analysis. Following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA), we searched PubMed, Cochrane, Embase, and Web of Science for studies treating refractory epilepsy with ANT‐DBS. Short‐term analysis was considered for studies with a mean follow‐up of 3 years or less. The following outcomes were assessed for data extraction: procedure responders and nonresponders, increased seizure frequency, complications, and procedure‐related mortality. Of 650 studies, 25 fit our inclusion criteria, involving 427 patients. Previous surgical treatments have been reported in 214 patients (50.1%) and a median average baseline seizure frequency of 64.9 monthly seizures. In the short‐term analysis, we observed a proportion of 67% (95% confidence interval [CI] 54%–79%) of responders and 33% (95% CI 21%–46%) of nonresponders. In addition, 4% (95% CI 0%–9%) of the patients presented increased seizure frequency. In the long‐term analysis, we observed 72% (95% CI 66%–78%) responders and 27% (95% CI 21%–34%) nonresponders. Moreover, there was a 2% (95% CI 0%–5%) increase in seizure frequency. No procedure‐related mortality was reported at any follow‐up. ANT‐DBS effectively treats refractory epilepsy, with lasting short‐term and long‐term benefits. It remains safe and efficient despite complications, showing no procedure‐linked fatalities, high patient responsiveness, and minimal increased seizures. Consistent results over time and low morbidity/mortality rates emphasize its worth. Further research is necessary to diminish the discrepancy among results.