This study aimed to assess the tolerability and safety profile of eslicarbazepine acetate (ESL).Placebo controlled, double-blind randomized controlled trials (RCTs) were enrolled by searching Pubmed, Embase, Cochrane Online Library, and clinicaltrial.gov. Studies evaluating the safety of ESL on any neurological disorders were included. Adverse events (AEs), serious AEs and AEs-related withdrawals were pooled by direct or indirect meta-analysis.A total of 4067 patients in 13 RCTs (5 for refractory partial epilepsy, 2 for bipolar I disorder, 1 for migraine, 1 for fibromyalgia, 2 for diabetic neuropathic pain, and 2 for post-herpetic neuralgia) were included. Meta-analysis revealed that ESL treatment had a higher incidence of serious AEs and AEs-related withdrawals than the placebo. Of 35 reported AEs, 13 were significantly associated with ESL treatment, including blurred vision, diplopia, vertigo, nausea, vomiting, fatigue, dizziness, somnolence, headache, rash, hyponatraemia, increased gamma-glutamyl transferase, and dysarthria. Subgroup analysis revealed that dizziness was the only AE significant at 400 mg/day, while diplopia, nausea, vomiting, dizziness, somnolence, rash, and hyponatremia at 800 mg/day, and blurred vision, diplopia, vertigo, nausea, vomiting, fatigue, dizziness, somnolence, headache, rash, and hyponatremia at 1200 mg/day were significant. Adjunctive use of ESL in refractory epilepsy significantly led to higher risk for vestibulocerebellar AEs than other disorders.ESL treatment was related to a range of AEs, especially at high doses or when used as adjunctive therapy in epilepsy. While the majority of AEs of ESL were related to the vestibulocerebellar system, hyponatremia and rash should also be noted by clinicians.