Objective: Epilepsy is a neurological disorder which often requires lifelong treatment with antiepileptic drugs (AEDs). Prolonged use of AEDs is associated with changes in vascular risk markers. Hence, the study was designed to evaluate the effect of older generation AEDs (carbamazepine and phenytoin) and newer generation AED (levetiracetam) monotherapy on the markers of vascular risk in epilepsy patients. Methods: This study was carried out in the neurology department of a tertiary care hospital for a period of 7 months. Clinical and biochemistry reports of 90 patients were collected in designed case report forms. All statistical analyses were performed using IBM Statistical Package for Social Sciences (SPSS) 17 and Graph Pad Prism 7.0. Results: We observed statistically significant changes in the liver enzyme level and glycated hemoglobin (HbA1c) in carbamazepine and phenytoin received groups. We did not observe any statistically significant difference in the above parameters in levetiracetam group but this group showed a significant change in complete blood count. Conclusion: Careful monitoring of the liver enzymes and HbA1c at regular intervals throughout the treatment course is considered necessary in epileptic patients undergoing long-term treatment with enzyme inducing AEDs.