Objective. Therapeutic pathomorphosis was studied basing on the results of treatment with antiepileptic drugs (AED) of different generations with the account of epilepsy etiology: symptomatic (SE), cryptogenic (CE) and idiopathic (IE). Material and methods. A long-term (8.5±3.0 years) prospective study included 404 patients, aged - 36.8±8.4 years, with SE (236 (58.4%) patients), CE (130 (32.2%) patients) and IE (38 (9.4%) patients). Results. Regardless of the causes of the disease, the most effective was monotherapy with new drugs (р<0.01), slightly less effective was monotherapy with traditional anticonvulsants, and then - treatment with combinations of traditional and new drugs. Positive therapeutic pathomorphosis was noted in IE (84.2% of patients in remission) in comparison with CE (p<0.05) and SE (p<0.01). In SE patients, the best treatment result (positive therapeutic pathomorphosis) was observed in those with vascular, including post-stroke, epilepsy, in which the remission of seizures was observed in 86.7% of cases (p<0.01). Negative therapeutic pathomorphosis of the disease with the development of pharmacoresistance was noted in epilepsy after traumatic brain injuries (p<0.05) and in mesial temporal sclerosis (p<0.05). Conclusion. The group of relatively resistant patients (14.4%) with fluctuating (remitting - relapsing) course of the disease was described.