Purpose <p>Epilepsy has been associated with alterations in cardiac repolarization, and the potential cardiac effects of antiseizure medications have raised increasing clinical interest. However, longitudinal pediatric data evaluating cardiac parameters during levetiracetam monotherapy remain limited. We aimed to prospectively assess electrocardiographic and echocardiographic changes during one year of levetiracetam monotherapy in children with genetic generalized epilepsy.</p> Methods <p>This prospective study included 52 children with newly diagnosed genetic generalized epilepsy, with generalized tonic–clonic seizures alone, receiving levetiracetam monotherapy. Standard 12-lead electrocardiography and transthoracic echocardiography were performed at baseline and after one year. Electrocardiographic parameters included PR, QTc, Tpeak–Tend (Tp–e), and Tp–e–based ratios. Echocardiographic measurements were analyzed using age- and body size–adjusted Z-scores.</p> Results <p>Fifty-two patients (mean age 9.31 ± 4.49 years; 42.3% female) completed follow-up. No statistically significant differences were observed between baseline and one-year electrocardiographic parameters, including PR (<i>p</i> = 0.725), QTc (399.80 ± 15.84 vs. 396.44 ± 20.00 ms; <i>p</i> = 0.143), Tp–e (<i>p</i> = 0.070), Tp–e/QT (<i>p</i> = 0.753), and Tp–e/QTc (<i>p</i> = 0.370). Echocardiographic indices, including LVDd Z-score (<i>p</i> = 0.535), IVSd Z-score (<i>p</i> = 0.099), and ejection fraction (68.13 ± 3.87% vs. 68.25 ± 3.86%; <i>p</i> = 0.666), showed no longitudinal changes.</p> Conclusions <p>In this prospective pediatric cohort of children with genetic generalized epilepsy, one year of levetiracetam monotherapy was not associated with adverse electrocardiographic or echocardiographic changes. These findings support a favorable cardiac safety profile of levetiracetam during one year of monotherapy in this pediatric population.</p>