Objective The study was performed to compare the efficacy and effect on quality of life of sodium valproate (VPA) sustained-release tablets versus topiramate (TPM) in newly diagnosed adult symptomatic epilepsy. Methods This is aprospective, randomized controlled trial on 200 patients newly diagnosed as adult symptomatic epilepsy in Sichuan Province People’s Hospital druing September 2014 to December 2016. The patients were randomly divided into VPA group (n=110) and TPM group (n=90). Then we evaluated the efficacy, retention rate, adverse reactions, and quality of life of the two groups after one year of treatment. Results The total effective rate of VPA group was 69.1%, and the rate of no seizures was 38.2%; the total effective rate of TPM was 62.2%, and the rate of no seizures was 42.2%. No statistically significant difference in the effective rate and no seizure rate was found between the two groups. There was no statistical difference in the retention rate between the two groups(69.1% vs. 65.6%, P>0.05) . The incidence of adverse reactions of VPA was significantly lower than that of TPM (9.1%vs. 20%, P<0.05). The quality of life of the two groups was significantly improved from baseline before treatment. VPA group showed significantly better performance than TPM group on mood and cognitive improvement (P<0.05). Conclusion ① There was no significant difference in efficacy and retention rate between VPA sustained-release tablet and TPM on adult patients with symptomatic epilepsy after one year's treatment; ② The incidence of adverse reactions of TPM group was significantly higher than that of VPA group; ③ VPA sustained-release tablets and TPM can significantly improve the overall quality of life of patients, and VPA sustained-release tablets is significantly better than topiramate on the improvement of emotional and cognitive function.