Background and Objectives: A high number of populations have epileptic disorder. The choice of drug is the important factor of treatment including that for acute and chronic epileptic seizure treatment. Selecting drug depends on its safety and efficacy. Monotherapy with drug is the safest approach of treatment. Objectives include, efficacy of LEV and VPA therapy, occurrence of adverse drug reactions. Methods: It is a prospective, observational, 9 month study in department of neurology in a 500 bedded tertiary care teaching hospital. The study population includes 90 subjects. Patient data entry form, informed consent form, Patient information sheet. The main study criteria is inpatients and out patients in the neurology department. They are selected according to specific inclusion and exclusion criteria. Results and Discussion: LEV and VPA are equally effective in the treatment of epileptic disorder. But LEV over VPA have some advantages include, its minimal protein binding, lack of hepatic metabolism, adverse reaction of the drug is comparatively better than the older antiepileptic drugs, except the psychiatric manifestations, and no significant drug interactions. These properties also provide better quality of life in persons with epilepsy compared with VPA. Conclusion: VPA show better efficacy than LEV in terms of seizure frequency, percentage reduction, responder rate. Safety of LEV is higher than VPA.