Objective To observe the efficacy and adverse reactions of pirenpanet in patients with refractory epilepsy treated with add-on therapy. MethodsForty-one patients with medically refractory epilepsy were selected from January 2021 to December 2021 in the Department of Epilepsy of Jiamusi Central Hospital, among which 25 males and 16 females. The self-control study was conducted before and after the treatment with pirenpanet. The observation period was 1 year, and the clinical efficacy, platelet, liver and kidney function and EEG discharge index were observed at 6 months and 12 months respectively. Changes in seizure frequency after treatment were divided into the following 3 groups: effective control: no seizure; effective: seizures reduced by 50% ~ 99%; Ineffective: < 50% reduction in seizures or exacerbation. Results Among the 41 patients with drug-refractory epilepsy, 8 (8/41, 19.51% P < 0.05) were seizure-free, 17 (17/41, 41.46% P < 0.05) were effective, and the total effective rate was (25/41, 60.98%); Sixteen cases (16/41, 39.02%) were ineffective. There were 31 children in 41 cases (31/41, 75.61%), of which 18 cases (18/31, 58.06%) were effective, 16 cases (16/31, 51.61%) had mental and motor retardation, and 8 cases (8/16, 50%) were effective; There were 10 adults (10/41, 24.39%) and 7 effective patients (7/10, 70%). After one year's treatment, the EEG changes of the patients were observed, and the abnormal discharge of 6 patients was reduced according to the discharge index, 2 patients had no abnormal discharge, and the other patients had no obvious EEG changes. Conclusion Pirenpanet is effective and safe as an add-on therapy for medically refractory epilepsy.