Background and Objective: For improving overall care in epileptic patients, careful evaluation of pharmacotherapy, seizure control, quality of life (QOL) and cost effectiveness are helpful but such data are relatively meagre from developing countries. The present study was undertaken to audit all these said factors with different drug combinations comparing older with newer drugs in the setting of a tertiary care epilepsy hospital in India. Methods: Forty patients were divided into four treatment groups, of ten each which were valproic acid + lamotrigine (Group-I), valproic acid+ clonazepam (Group-II), oxcarbazepine + clobazam (Group-III) and phenobarbitone + phenytoin (Group-IV), based on most commonly used dual therapy in local clinical practice. The patients were followed at monthly intervals for six months. Effi cacy was assessed by reduction in seizure frequency, QOL was assessed by using an adapted version of 31- items questionnaire QOLIE-31 (quality of life in epilepsy) and cost effectiveness was calculated as ratio of direct cost of medicine and improvement in quality of life. Results: There was a signifi cant reduction in seizure frequency and improvement in QOL in all four groups at 2nd and 6th months. Cost-effectiveness analysis at the end showed that group-IV paid the least for same improvement in QOL. Conclusion: Older drugs are equally effi cacious as compared to newer in controlling seizure frequency and improving QOL, but are more cost effective.