Introduction: Patients with epilepsy (PWE) have poor quality of life (QOL) due to several events. This study is aimed to determine the effect of different anti-epileptic drugs (AEDs) monotherapy; Lamotrigine (LTG), Carbamazepine (CBZ) and Sodium Valproate (VPA) on QOL of newly diagnosed idiopathic generalized epilepsy. Patients and Methods: Thirty-six newly diagnosed patients with idiopathic generalized epilepsy from outpatient’s clinic of Assuit university Hospitals. According to AEDs treatment they were randomly classified into three groups with ratio 1:1:1: LTG, CBZ and VPA groups (N=12 for each). Quality of Life of these patients, using Epilepsy Inventory version 1.0 (QOLIE-31), and serum level of AEDs were assessed at baseline, after one and three months of treatment. Results: There was no significant difference between demographic and clinical data of the studied AEDs groups at baseline and there was a significant decline in frequency of seizures after three months, with significant improvement in overall score of QOLIE-31, social function and emotional well-being subscales, but Energy/Fatigue subscale showed significant improvement in LTG and CBZ groups without changes in VPA group. while the medication effect and overall QOL subscales showed significant improvement in LTG and VPA groups without improvement in CBZ group. The cognitive subscale of QOLIE-31 showed significant deterioration in CBZ group that was not found in LTG or VPA groups. Conclusion: AEDs monotherapy improve QOL of newly diagnosed Epileptic patients while LTG monotherapy was significantly more effective and tolerated for improving several aspects of QOL than VPA or CBZ monotherapy in newly diagnosed epileptic patients after 3 months of treatment.