Objective. To optimize drug treatment in early (6 months) and late (up to 3 years) stages of postoperative period and to study its efficacy. Material and methods. There were selected 72 patients with resistant epilepsy and epileptic encephalopathy symptoms from 467 patients operated for epilepsy. Results. By the end of a 3-year follow-up observation, we found the reduction in seizure frequency and seizure control in 66.3% of patients; regression of EEG paroxysmal activity in 56.8% and reduction in mental disorder symptoms (anxiety and depression) in 12.7%. Conclusion. The data obtained substantiate the necessity to optimize antiepileptic and pathogenetic drug treatment of patients with resistant epilepsy and encephalopathy symptoms during the 3-year postoperative period.