Background: The lifetime prevalence of epilepsy varies between 3.5 and 10.7 per 1000 individuals in developed countries, and from 0.9 to 74.4 per 1000 individuals in Asia, sub-Saharan Africa, and Latin America. In adolescents, the prevalence of epilepsy is estimated to be 1.5 to 2%. Purpose: The purpose of this study was to examine the clinical characteristics of adolescents with epilepsy (AWE) and highlight the differences between childhood-onset epilepsy and adolescent-onset epilepsy. Additionally, the study aimed to assess the level of self-stigma and depression, as well as their impact on adherence to antiseizure medication (ASMs). Methods: This cross-sectional study was conducted at the Epilepsy Clinic at Kasr Al-Ainy Hospitals. Patients underwent a thorough evaluation of their seizure history, as well as completed the Adherence to Refills and Medications Scale (ARMS), Kilifi Stigma Scale for Epilepsy (KSSE), and Patient Health Questionnaire-9 (PHQ-9) to assess depression. Results: A total of 136 AWE were included in the study, consisting of 82 males and 54 females with a median age of 15 and an interquartile range of 13-17. Most patients (54 %) had focal onset seizures, while the remaining 46 % had generalized onset seizures. Of the total sample, 87 (64 %) achieved seizure control for at least one year and are currently taking ASMs. However, only 60 % of the patients were found to be adherent to their ASMs. Fourteen patients (17.2 %) met the criteria for drug-resistant epilepsy. Interestingly, patients with adolescent- onset epilepsy were significantly more adherent to their ASMs compared to those with childhood-onset epilepsy (P=0.01). Additionally, the adherent group had significantly lower scores on KSSE and PHQ-9 compared to the non-adherent group (P=<0.0001 for each). Furthermore, there was a positive correlation between scores on the KSSE and PHQ-9 (P<0.001). Conclusion: Depression and self-stigma are significant barriers to adherence among adolescents with epilepsy. These findings highlight the need to involve psychiatrists and epileptologists in epilepsy transition programs.