Background: Epilepsy is considered as one of the most common serious neurological conditions. The prevalence of childhood epilepsy is approximately 3.5 to 7 per thousand children. Drug resistance is one of the major problems facing the treatment of epilepsy even with the new drugs and medical science progress. Assessment of the risk factors of epilepsy drug treatment failure in epileptic children may be determine the (risk factor or cause) of drug resistance epilepsy. Objectives: This study aimed to identify the most important factors of drug treatment failure of epilepsy in children. Patients and Methods: A total of 120 epileptic children were recruited from Outpatient Clinics, Zagazig University Hospitals.All patients were subjected to Full history taking,thorough general and neurological examination. Then they were classified according to the response of treatment into controlled and uncontrolled groups. Results:Their ages ranged between 2 and 18 years including 74 males (61.7%) and 46 females (38.3%). About 44.2% of patients were on polytherapy while 55.8% were on monotherapy .There was 47 patients(39.2 %) controlled on treatment while 73 patients (60.8 %) were uncontrolled.There was significant association between focal seizures, generalized tonic colonic seizures, abnormal EEG, polytherapy and bad combination of drugs on one hand and poor control of seizures on the other hand . Conclusion: Accurate diagnosis ,good choice of antiepileptics with appropriate dose and combinations (when indicated) can help better control of epilepsy.