Background: Although Ablation Index (AI)-guided ablation facilitates creation of lesions of consistent depth, pulmonary vein (PV) reconnection is still commonly observed after AI-guided pulmonary vein isolation (PVI). The present study aimed to investigate the impact of local left atrial wall thickness on the incidence of acute PV reconnection after AI-guided atrial fibrillation (AF) ablation. Methods and results: Seventy patients (63% paroxysmal AF, 67% male, mean age 63 ± 8 years) who underwent preprocedural CT imaging and AI-guided AF ablation were studied. Occurrence of acute PV reconnection after initial PVI was assessed after a 30-minute waiting period. Ablation procedures were retrospectively analyzed and each ablation circle was subdivided into 8 segments. Minimum AI, force-time integral, contact force, ablation duration, power, impedance drop and maximum interlesion distance were determined for each segment. PV antrum wall thickness was assessed for each segment on reconstructed CT images based on patient-specific thresholds in Hounsfield Units. Acute reconnection occurred in 27/1120 segments (2%, 15 anterior/roof, 12 posterior/inferior) in 19/140 ablation circles (14%). Reconnected segments were characterized by a greater local atrial wall thickness, both in anterior/roof (1.87 ± 0.42 vs. 1.54 ± 0.42 mm; p < 0.01) and posterior/inferior (1.43 ± 0.20 vs. 1.16 ± 0.22 mm; p < 0.01) segments. Minimum AI, force-time integral, contact force, ablation duration, power, impedance drop and maximum interlesion distance were not associated with acute reconnection. Conclusions: Local atrial wall thickness is associated with acute pulmonary vein reconnection after AI-guided PVI. Individualized AI targets based on local wall thickness may be of use to create transmural ablation lesions and prevent PV reconnection after PVI.