Introduction: Epilepsy is a neurological disease with the highest prevalence in paediatrics. Using anti-epileptic drug as monotherapy is the first-line therapy for paediatrics based on risk-benefit ratio consideration in the patients effectiveness and adverse drug reaction of anti-epileptic monotherapy drug for the cognitive function in paediatric patients. Objectives: The aim of the study is to assess effectivity and adverse drug reaction of anti-epileptic monotherapy drug for the cognitive function in paediatric patients. Methods: This was a cross sectional study. This study used patients from the Dr. Sardjito hospital’s outpatient paediatric unit’s Neurology division from May to July 2013 and May to June 2019 to select the subjects. Patient questionnaires and medical records provided the data that was used. Effectiveness was assessed by seizure severity with Hague Seizure Severity Scale (HASSS) questionnaire and seizure frequency, while adverse drug reactions in cognitive function were assessed by the PESQ (Pediatric Epilepsy Side Effect Questionnaire) instrument. Results: In total, 29 patients received monotherapy, with 26 patients (89.66%) receiving valproate, two (6.89%) receiving phenytoin, and one (3.45%) receiving phenobarbital. A total 89.66% of patients did not have severe seizures, but 6.90% had moderate seizures. The cognitive function of epileptic patients with co-morbidities receiving valproate monotherapy had moderate (27.59%) and severe (20.69%) side effects. The adverse drug reaction experienced in epileptic patients without co-morbidities using valproate was with the cognitive function, with 6.89% of patients experiencing severe effects, 13.79% moderate and 20.69% mild effects. Conclusion: While anti-epileptic monotherapy can control seizures in children, the commonly prescribed valproate can impair cognitive function, especially in those with co-morbidities.