Objective To observe the effectiveness and safety of topiramate, sodium valproate and carbamazepine in the treatment of post-encephalitis epilepsy, and to provide reference for the rational use of drugs in clinical practice. The patients were randomly divided into 3 groups: 40 cases of topiramate, 40 cases of sodium valproate, and 40 cases of carbamazepine, and each group was treated with corresponding drugs for 12 months. The patients with adverse reactions were treated with intravenous blood to detect the blood concentration and monitor the toxic blood concentration, and the results were compared. The total effective rate was 92.5% in the topiramate group, 70.0% in the sodium valproate group, and 62.5% in the carbamazepine group, and the difference between the three groups was statistically significant (0.05). It is concluded that topiramate is preferred for the treatment of patients with post-encephalitic epilepsy, followed by sodium valproate and carbamazepine, and individualized dosing regimens based on blood concentration monitoring can improve the safety of dosing.