Background and aim: The GORE^® CARDIOFORM (GCO) septal occluder is an atrial septal defect/patent foramen ovale closure device with theoretical advantages over other commercialized devices thanks to its softness and anatomical compliance. Our aim was to evaluate the short- and medium-term electrocardiographic changes after percutaneous ASD closure with GCO in a pediatric population. Methods: We enrolled 39 patients with isolated ASD submitted to trans-catheter closure from January 2020 to June 2021. ECG was performed before, at 24 h and 6 months after the procedure. P wave dispersion, QTc and QTc dispersion were calculated. ECG Holter was recorded at 6 months after implantation. Results: Patients’ age and body surface area (BSA) were 8.2 ± 4.2 years and 1.0 ± 0.3 m² respectively. At the baseline, mean P wave dispersion was 40 ± 15 msec and decreased at 24 h (p < 0.002), without any further change at 6 months. At 24 h, PR conduction and QTc dispersion significantly improved (p = 0.018 and p < 0.02 respectively), while the absolute QTc value considerably improved after 6 months. During mid-term follow-up, QTc dispersion remained stable without a significant change in PR conduction. The baseline cardiac frequency was 88.6 ± 12.6 bpm, followed by a slight reduction at 24 h, with a further amelioration at 6 months after the procedure (87.3 ± 14.2, p = 0.9 and 81.0 ± 12.7, p = 0.009, respectively). After device deployment, two patients developed transient, self-limited junctional rhythm. One of them needed a short course of Flecainide for atrial ectopic tachycardia. No tachy/brady-arrhythmias were recorded at the 6-month follow-up. ASD closure resulted in a marked decrease in right heart volumes and diameters at 6 months after percutaneous closure. Conclusions: Percutaneous ASD closure with the GCO device results in significant, sudden improvement of intra-atrial, atrio-ventricular and intraventricular electrical homogeneity. This benefit persists unaltered over a medium-term follow-up. These electrical changes are associated with a documented positive right heart volumetric remodeling at mid-term follow-up.