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BACKGROUND Resistance to antiepileptic drug treatment increases the risk of comorbidities and mortality due to a cardio-autonomic imbalance and left ventricular (LV) dysfunction. OBJECTIVE To assess the prevalence of LV dysfunction and cardio-autonomic imbalance in children with drug-resistant epilepsy (DRE). PATIENTS AND METHODS This cross-sectional study included 40 children with DRE and 40 healthy age- and sex-matched controls. LV function was evaluated by M-mode, two-dimensional, pulse-wave Doppler echocardiography, and tissue Doppler imaging (TDI). Cardio-autonomic function was assessed by 24 -h Holter monitoring of heart rate variability. RESULTS All time domain measures were significantly lower in the epilepsy group than in the control group (all Ps<0.01). Additionally, the mean high frequency (HF) parameters were significantly lower (P = 0.035), whereas the mean low frequency (LF) parameters and the LF/HF ratio were significantly higher (P < 0.001) in the epilepsy group than in the control group. LV function did not differ between groups regarding all standard echocardiographic parameters. There was evidence of subclinical LVdysfunction by tissue doppler among the epileptic group, as evidenced by the elevated Myocardial Performance Index, isovolumetric relaxation time and mitral E/Em ratio. There was no significant correlation between the duration of epilepsy or seizure frequency with any cardiac abnormality. CONCLUSIONS Children with DRE exhibited cardio-autonomic and subclinical LV dysfunction, independent of the duration of epilepsy, frequency, and seizure type.