OBJECTIVE : This study was designed to assess the efficacy of electroanatomic-mapping (EAM)-guided cardioneuroablation (CNA) vs combined approach for vasovagal syncope (VVS). METHODS : Twenty patients with VVS refractory to conventional treatments who underwent CNA in our institution were enrolled in the study. Twelve of these patients underwent recently introduced EAM-guided CNA using signal-based approach while 8 patients underwent combined CNA using a combination of high-frequency stimulation and spectral analysis. Both atria and coronary sinus were divided into seven segments to categorize distribution of ganglionated plexi in ablation sites. Clinical responses were evaluated and compared in terms of prodromal symptoms and syncope recurrence rates. Electrophysiological parameters and heart rate variability (HRV) analysis were used to evaluate procedural response. RESULTS : Procedural endpoints were achieved in all cases without any serious adverse events. Compared with the combined approach group, EAM-guided CNA was related to a shorter procedure and fluoroscopy times (p < 0.001). The mean number of ablation points in each anatomical segment was comparable between groups. The prodromal symptoms demonstrated a significant and comparable decrease after CNA. Median event-free survival was comparable between groups (χ2 = 0.03, p = 0.87). There was no new syncopal episode in any case at the end of 6-month follow-up. In the combined approach group, new syncope episodes occurred in two cases after 12-month follow-up. HRV parameters indicating parasympathetic activity were comparably decreased after ablation in both groups. CONCLUSIONS : This pilot study shows that EAM-guided CNA strategy is feasible and safe in VVS patients resistant to conventional therapies.