Background <p>This study aimed to assess cardiac ischemic changes in pediatric patients with drug-resistant epilepsy (DRE) and to assess the predictive value of ictal serum level of heart-type fatty acid binding protein (H-FABP) in identifying early ischemic changes.</p> Methods <p>This cohort study was conducted on 30 children with DRE as group I, 30 children with controlled epilepsy as group II, and 30 healthy children of matched age and sex as group III. Electrocardiographic examination was performed to detect cardiac changes during seizures. H-FABP was measured during (ictal) and 24 h after control of seizure (postictal) in the DRE group, and once for groups II and III.</p> Results <p>Ictal tachycardia was observed in 28 patients (93.3%) of DRE patients, while ictal bradycardia occurred in only two patients (6.7%). Ischemic changes were noted in 10 patients (33.3%). The ictal serum level of H-FABP in children with DRE was significantly higher than that in the controlled epilepsy and the healthy control groups, and positively correlated with seizure duration and frequency and heart rate. Although post-ictal H-FABP levels declined, the difference was not statistically significant. The ictal level of H-FABP demonstrated a good predictive value for cardiac ischemia in children with DRE, with a cut-off value of &gt; 1205.7 pg/ml, showing a sensitivity of 91.67% and a specificity of 83.33%.</p> Conclusion <p>Pediatric patients with DRE are at a considerable risk of cardiac ischemia. H-FABP serves as a promising early biomarker for ischemic cardiac injury in these patients.</p>