ObjectiveTo systematically review the efficacy and safety of new anti-epileptic drugs in the treatment of epilepsy. MethodsPubMed, EMbase, The Cochrane Library, CNKI and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) of new anti-epileptic drugs rufinamide, zonisamide, and perampanel in the treatment of epilepsy from January 2006 to May 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; then, meta-analysis was performed by using RevMan 5.3 and Stata 16.0 software. ResultsA total of 16 RCTs involving 4 382 patients were included. The results of meta-analysis showed that the effective rate (RR=1.66, 95%CI 1.45 to 1.89, P<0.000 01) and seizure-free rate (RR=2.82, 95%CI 2.01 to 3.96, P<0.000 01) in new anti-epileptic drugs group were higher than those in the control group, while it did not increase the serious adverse events (RR=0.95, 95%CI 0.72 to 1.27, P=0.75). ConclusionCurrent evidence shows that new anti-epileptic drugs have trends of better effectiveness, and their safety is satisfactory. Due to limited quality and quantity of the included studies, more high-quality studies are needed to verify above conclusion.