BACKGROUND: Medication adherence is a fundamental determinant of effective treatment. However, people with epilepsy have poor compliance with their treatment because of the chronic nature of the disease. Limited studies have been conducted to address antiepileptic medication adherence in Africa, including Ethiopia. Thus, the aim of this study was to assess antiepileptic drug adherence and its asociated factors among patients with epilepsy attending outpatient department of Amanuel Mental Specialized Hospital.METHODS: A cross-sectional study design was conducted on 439 patients with epilepsy in Amanuel Mental Specialized Hospital. Medication adherence reporting scale-5 (MARS-5) was used to assess adherence to antiepileptic drugs. The Oslo social support, Jacob perceived stigma scale, and hospital anxiety and depression scale (HADS) were the instruments used to assess associated factors. Simple and multiple linear regression analysis models were fitted. Then, the adjusted unstandardized beta (β) coefficient at a 95% confidence level was used.RESULTS: The mean(SD) score of antiepileptic medication adherence was 16.38(±3.76) with 95%CI:(16.03, 16.72). Depressive symptoms (β= -1.35, 95% CI: (-2.04, -0.65)), anxiety symptoms (β=-1.12,95%CI:(-1,79,-0.44), perceived stigma (β= -1.64, 95% CI:-2.16,-1.12), being single (β=-0.67, 95%CI:-1.20,-0.14), presence of seizure per month(β=-2.11,95% CI: (-2.81,-1.41) and antiepileptic drug adverse effect(β=-0.07,95%CI:-0.11,-0.03) were factors associated with anti-epileptic medication adherence.CONCLUSION: The results suggest that the mean score of adherence to antiepileptic drugs was poor as compared to other settings. Antiepileptic medication adherence screening tool should be included in the patient’s treatment protocol.KEYWORDS:Antiepileptic medication; Adherence; Epilepsy