Epilepsy is a major non-communicable disorder. Choice between switching to another drug and combining is still debatable when the first antiepileptic drug is ineffective in controlling seizure. Polytherapy usually related with the appearance of adverse effect. This cross sectional study was conducted in Neurology Policlinic with 83 epilepsy patients, consisting of 37 patients used monotherapy and 46 patients used polytherapy. The most common adverse effect was fatigue. Statistical analysis using chi square test showed statistically significant between monotherapy and polytherapy patients against fatigue (p value >0.05). In conclusion, polytherapy is related with the appearance of adverse effect in epilepsy patients.