Partial and generalized seizures often affect autonomic functions during seizures, and interictal and postictal periods. We investigated possible interictal electrocardiographic abnormalities in patients with generalized tonic-clonic seizures (GTCS), together with evaluating any structural heart changes by echocardiography in these patients in comparison with healthy controls. We studied 120 definite GTCS patients (76 males and 44 females) who are neither diabetic nor under any medical treatment, and 60 healthy controls with a mean age of 25.2 ± 9.3 and 27.3 ± 7.5 years; respectively. Resting systolic and diastolic arterial blood pressures were measured, and standard 12-lead electrocardiograms and a 2-dimensional echocardiographic examination were performed. In univariate analysis, GTCS patients (compared to controls) had significantly lower means of PR interval (147.2 ± 18.6 versus 153.8 ± 22.6 msec; P = 0.037), QT interval (362.8 ± 22.9 versus 379.9 ± 29.3 msec; P < 0.001), and QTc interval (425.5 ± 20.7 versus 441.6 ± 19.9 msec; P < 0.001) but significantly higher mean left atrial diameter (3.49 ± 0.64 versus 3.09 ± 0.45 cm; P < 0.001). After adjusting for age, gender, and body mass index in a multivariate adjusted logistic regression model, left atrial diameter (OR = 3.941 [1.739 - 8.932]) and QTc (OR = 0.924 [0.895 - 0.954]) were significantly and independently associated with GTCS. In conclusion, patients with epilepsy may be predisposed to disturbances of autonomic functions with subsequent cardiac arrhythmias due to the effects of recurrent seizures on cardiac microstructure. Further work is needed to stratify the risk of sudden unexplained cardiac death (SUDEP) on the basis of interictal autonomic parameters to improve prognosis.