BACKGROUND: Epilepsy is a major neurological disorder, typically managed with Anti-Seizure Medication (ASM). Nevertheless, a substantial 30 % of patients did not respond satisfactorily to ASMs, classifying their condition as Drug-Resistant Epilepsy (DRE). Vagus Nerve Stimulation (VNS) was recommended as a potential solution. OBJECTIVE: To evaluate clinical efficacy of VNS on patients with DRE in reduction of seizures through a systematic review and meta-analysis using a random effects model. METHODS: A systematic search was done from PubMed, ScienceDirect, Cochrane Library and Google Scholar databases on observational studies and randomized controlled trials (RCTs) for the clinical effectiveness of VNS among DRE patients. A meta-analysis was performed to obtain the pooled estimate of the clinical effectiveness of VNS in terms of seizure reduction and the odds ratio (OR) for patients achieving >
50 % seizure reduction. Heterogeneity was assessed using visual inspection of forest plots and I RESULTS: A total of 1023 articles were retrieved from the electronic search. After removing duplicates, non-relevance and non-availability of efficacy data, 28 articles were included in the final analysis. Of these, 9 are RCTs and 19 are observational studies. The pooled estimate of >
50 % seizure reduction was 0.46 (95 % CI: 0.40-0.51) and the pooled estimate of the OR comparing >
50 % vs ≤ 50 % seizure reduction was 0.76 (95 % CI: 0.44-1.29). CONCLUSION: Our meta-analysis showed that 46 % of DRE patients have experienced ≥ 50 % seizure reduction with VNS treatment. It should be considered in patients in whom ASM has failed or who continue to experience seizures after medication.