Aims: This systematic review and meta-analysis of randomized controlled trials (RCTs) systematically explored the effectiveness and safety of lamotrigine for absence seizures in children and adolescents. Methods: Keywords searches were conducted in Pubmed Embase Cochrane Central Register of Controlled Trials Wanfang CNKI from inception through March 2019. The RCTs comparing lamotrigine with other drugs and/or placebo for the treatment of absence seizures in children and adolescents were considered in this study. The study was conducted adhering to PRISMA guidelines. Results: Eight RCTs (n = 787) were included in our study. Among these studies, one study (N = 45 patients) used placebo as a control and seven studies (N = 742 patients) used positive drug controls. For effectiveness, there was significant difference between lamotrigine and valproate [OR = 0.42, 95%CI (0.28–0.63), I2 = 0%] or ethosuximide [OR = 0.34, 95%CI (0.22–0.53), I2 = 0%]. For adverse effects (AEs), there was no significant difference between lamotrigine and valproate [OR = 1.17, 95%CI (0.59, 2.32), I2 = 0%] or ethosuximide [OR = 0.75, 95%CI (0.47, 1.19), I2 = 92%], and the most common adverse effects of lamotrigine were Rash (7.88%), Fatigue (6.50%) and Headache (6.50%). Conclusions: According to current evidence, LTG is less effective than VPA and ESM, however, based on its relative safety, LTG might be reasonably tried as initial therapy in children and adolescents at risk of significant adverse effects from VPA and ESM, and future well-designed studies are needed to confirm our findings. © 2019 Elsevier Ltd