Abstract Background Personalized radiofrequency (RF) catheter ablation for paroxysmal atrial fibrillation (PAF), tailoring the ablation index (AI) to the local left atrial wall thickness (LAWT), has proven to be an efficient procedure with high arrhythmia-free survival rates. However, to date, only monocentric experiences have been reported in the literature. Purpose The present study sought to report a multicenter experience in order to assess the safety, efficacy, and efficiency, of a LAWT-guided personalized pulmonary vein isolation (PVI) approach for PAF ablation (ClinicalTrials.gov, NCT04218604). Methods We conducted an international multicenter prospective study at five tertiary hospitals (two in Spain, one in Italy, one in Germany, and one in the United States). Consecutive patients referred for first-time RF catheter ablation of PAF were prospectively enrolled from November 2020 to September 2022. In all patients a three-dimensional map of LAWT were obtained from preprocedural multidetector computed tomography (MDCT)-derived data postprocessing. LAWT was categorized into 1 mm layers and AI was titrated according to the LAWT. All procedures were performed under general anesthesia, utilizing high-rate low-tidal volume (HR-LTV) ventilation (Figure 1). All antiarrhythmic drugs were discontinued following the 3-month blanking period. The primary endpoint was freedom from any documented sustained atrial arrhythmia at 12-month follow-up, regardless of symptoms. Results One hundred and nine patients (60.1±9.4 years, 64.2% male) were prospectively enrolled. The mean LA diameter was 38.7±5.8 mm and the mean left ventricular ejection fraction was 60.7±4.7%. The median procedure time was 61.7 minutes (IQR 48.4–83.8), and the median RF application time was 13.9 minutes (IQR 12.3–16.8). The mean number of VisiTags was 63.2 ± 18. First-pass PVI was achieved in the 83.5% of patients. The median fluoroscopy time was 61.5 seconds (IQR 22.5–197.5). In 94 (86.2%) patients, ablation was performed with a single femoral venous puncture. At 12-month follow-up, the rate of freedom from any documented atrial arrhythmia was 93.4% (Figure 1). Two (1.8%) patients died during follow-up, one from unknown cause three months after the procedure, and another from complications following multiple trauma after falling from a ladder. One patient (0.9%) developed femoral artery pseudoaneurysm, with no other serious procedure-related complications. Conclusion The Ablate-by-LAW multicenter study proved that a personalized PAF ablation protocol, tailoring the AI to the local LAWT is highly efficient and achieved a high acute first-pass PVI rates. The study reported a high 12-month survival-free from any documented sustained atrial arrhythmias, exceeding 90%, and an exceptionally low incidence of serious procedure-related complications.