OBJECTIVES: Perampanel (PER) is the first orally active α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist approved for the adjunctive treatment of partial-onset seizures in patients with epilepsy aged 12 years and older. While the regulatory approval was on the basis of 3 RCTs, which demonstrated the efficacy and acceptable safety of perampanel relative to placebo, for the purpose of funding and health technology assessment decisions comparisons to other similar AED are necessary.The aim is to compare the clinical efficacy and tolerability of PER relative to other recently approved AEDs (lacosamide (LCM), retigabine (RTG), and eslicarbazepine (ESL)) for the adjunctive treatment of partial onset seizures with or without secondarily generalization. METHODS: A systematic literature review was conducted to identify all RCTs of PER and selected AEDs.  EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials from 1998 to September 2011, abstracts from selected 2010 and 2011 conferences, reference lists of included studies and unpublished study reports were searched.  The odds-ratio for three outcomes: “>50% reduction in seizure frequency”, “seizure freedom” and “withdrawal due to adverse events” were estimated using fixed- and random-effects Bayesian NMA models. RESULTS: Twelve RCTs (3 PER, 3 LCM, 3 RTG and 3 ESL) met the inclusion criteria. In the analysis for “>50% reduction in seizure frequency”, all AEDs performed significantly better than placebo with odds-ratio for PER being similar to the other comparators.  In the analysis for “seizure freedom”, all AEDs except LCM performed significantly better than placebo.  In the analysis for “withdrawal due to adverse events” PER had the lowest odds-ratio compared to other AEDs. No significant difference was observed in any of the three outcomes between PER and the other AEDs when compared against each other.  CONCLUSIONS: Compared with other licensed adjunctive AEDs, perampanel offers similar clinical efficacy and tolerability profile.