AbstractEpilepsy is a chronic neurological disease with a variable therapeutic response. To design effective treatment strategies for epilepsy, it is important to understand treatment responses and predictive factors. However, limited data are available in Africa, including Ethiopia. The aim of this study was therefore to assess treatment response and identify prognostic predictors among patients with epilepsy at Jimma university medical center, Ethiopia. We conducted a retrospective cohort study of 404 newly diagnosed adult epilepsy patients receiving antiepileptic treatment between May 2010 and May 2015. Demographic, clinical, and outcome data were collected for all patients with a minimum follow-up of two years. Cox proportional hazards model was used to identify predictors of poor seizure remission. Overall, 261 (64.6%) of the patients achieved seizure remission for at least one year. High number of pre-treatment seizures (adjusted hazard ratios (AHR) = 0.64, 95% CI: 0.49–0.83) and poor adherence (AHR = 0.57, 95% CI: 0.44–0.75) were significant predictors of poor seizure remission. In conclusion, our study showed that only about two-thirds of patients had achieved seizure remission. The high number of pre-treatment seizures and non-adherence to antiepileptic medications were predictors of poor seizure remission. Patients with these characteristics should be given special attention.