Introduction: Improving the health-related quality of life of patients with epilepsy has a prominent role in the management of sickness. In this study, we aim to compare health-related life quality (QOL) between male and female active epilepsy patients and investigate the clinical factors that may impair their quality of life.Methods: Total 172 patients (82 female, 90 male) which are traced about their diagnosis of active epilepsy are included in this study. All of the subscales related to the Quality of Life in Epilepsy Inventory (QOLIE-31), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) are compared between the female and male patients with epilepsy. In addition, the clinical factors associated with the illness and the topics about whether there are relations between quality of life (QOL) and psychiatric symptoms or not are evaluated separately for both genders.Results: It is examined that there is a considerably decrease in the subscales of female with epilepsy related to the overall (p= 0.054), social (p= 0.041) and cognitive functions (p= 0.043) of the QOLIE-31 test compared to male with epilepsy. It is determined in the correlation analysis of male patients that all of the QOLIE-31 subscales are negatively correlated with seizure frequency. Negatively correlation with seizure frequency is examined in all of the categories except for the subscales related to the emotional well-being and medication effects. Additionally, it is confirmed that there is a significant correlation between BDI and BAI scores and seizure frequency in both groups.Conclusion: These results suggest that the rise in epileptic seizure frequency may affect women’s social and cognitive skills in the course of the disease. Moreover, it is seen that the rise in epileptic seizure frequency is the most important clinical factor associated with the decline in QOL of people with epilepsy. Hence, gender-focused studies and clinical approaches may cause the improvement in the treatment modalities and QOL in epilepsy.Keywords: Epilepsy, Gender, Active Epilepsy, Health-related Quality of Life