Abstract: Objective To investigate the efficacy of lamotrigine(LTG)combined with small dose valproic acid(VPA)in the treatment of newly diagnosed epilepsy. Methods A total of 86 newly diagnosed epilepsy patients were randomly divided into single drug group(n=43)and combined group(n=43). Single drug group was treated with small dose VPA, and combined group was treated with LTG and small dose VPA. The therapeutic effect of epilepsy, changes of neurocognitive function and occurrence of adverse drug reactions(ADR)were compared between two groups. Results After treatment, the frequency of epileptic seizures, duration of seizures, epileptiform discharges and involvement leads decreased significantly in both groups(P<0.05), and the above indexes in the combined group were significantly better than those in the single drug group(P<0.05). After treatment, the score of Montreal Cognitive Assessment Scale(MoCA)in the combined group was significantly higher than that in the single drug group(P<0.05), and the total clinical effective rate was significantly higher than that in the single drug group(P<0.05). The incidence rate of ADR in single drug group and combined group was 11.63% and 18.60% respectively, and there was no significant difference between the two groups(P>0.05). Conclusion LTG combined with small dose VPA, with higher safety, can significantly improve the clinical symptoms and neurocognitive function of epilepsy, enhance the clinical efficacy.