Background Epilepsy is one of the commonest chronic neurological disorders with serious health consequences. Treatment adherence is one of the determinants of seizure control. This study was designed to determine factors affecting antiepileptic drug adherence among children with epilepsy. Methods A cross sectional study was conducted on 192 children with epilepsy (≤14 years of age) on follow-up at a pediatric neurology clinic in Southern Ethiopia from January 1st to August 30th, 2019. Medication Adherence was measured using the eight-item Morisky’s medication adherence scale. Logistic regression analysis was done to determine factors associated with antiepileptic drug adherence. Result One hundred twenty-five (65%) of the study subjects were adherent to their medication. On multivariable analysis, factors predictive of good adherence included family size of ≤5 [AOR = 2.34, (95% CI: 1.07, 5.10); P = 0.03] and duration of epilepsy (<1year [AOR = 5.83, (95% CI: 1.48, 22.92); P = 0.012] and 1-2year [AOR = 4.58, (95% CI: 1.12, 18.77); P = 0.035]). Monthly family income of <1000 Ethiopian Birr [AOR = 0.18, (95% CI: 0.06, 0.61); P = 0.005] and presence of seizure attack in the past 3months [AOR = 0.23, 95% (CI: 0.10, 0.55); P = 0.001] predicted poor antiepileptic drug adherence. Conclusion Adherence to antiepileptic drugs in children is low in our setting; low family income and occurrence of seizures while on treatment predicted poor adherence. Supplying free antiepileptic drugs to poor children and regular provision of information about expected treatment response to children with epilepsy and their caretakers may help improve adherence.