AbstractEpilepsy is a major public health problem worldwide. Despite multiple drug therapies, people with epilepsy continue to have frequent seizures. There is a dearth of data on epilepsy treatment outcome and associated factors in our setting. Therefore, the aim of this was to assess treatment outcome and associated factors among epileptic patients on follow up at the neurologic clinic of Ayder comprehensive specialized hospital, Ethiopia. A cross-sectional study was conducted on randomly selected epileptic patients. Data were collected through patient interview and review of medical records. Epilepsy treatment outcome was evaluated in terms of seizure control status in the last one year follow up period. Binary logistic regression analysis was performed to identify predictors of treatment outcome. A total of 270 patients were included. Of whom, 46.6% had controlled seizures. Whereas, 38.5%, 8.8%, and 5.9% had experienced seizure attacks 1–5 times, 6–10 times, and greater than 10 times, respectively. Alcohol consumption [adjusted odds ratio [(AOR): 14.87, 95% confidence interval (CI): 3.25–68.11], negative medication belief [AOR: 3.0, 95%CI: 1.31–6.71], low medication adherence [AOR:11.52, 95%CI: 3.25–40.82], and presence of comorbidities [AOR: 10.35, 95%CI: 4.40–24.40] were predictors of uncontrolled seizure. Our finding revealed that more than half of the epileptic patients had uncontrolled seizure. Epileptic patients with a negative medication belief, comorbidities, low medication adherence, and those who consume alcohol were more likely to have uncontrolled seizure. Therefore, more emphasis should be given to these patients.