Abstract Backgrounds Cryoballoon pulmonary vein isolation (PVI; Cryo-PVI) has comparable results to conventional radiofrequency PVI (RF-PVI) in patients with atrial fibrillation (AF). However, Cryo-PVI using a 28-mm cryoballoon has limitations for wide circumferential PVI or extra-pulmonary vein (PV) trigger (ExPVT) ablations. We compared long-term outcomes of Cryo-PVI and RF-PVI in patients without ExPVT and explored the potential electroanatomical mechanisms. Methods We identified 2,160 patients who underwent de novo AF ablation. After propensity score matching for age, sex, AF type, and left atrial (LA) diameter for patients without ExPVT (female 24.6%, mean 61.8years old, paroxysmal AF 53.2%), we compared rhythm outcomes between 403 Cryo-PVI and 403 RF-PVI procedures, considering AF type and LA size. We determined the LA diameter cutoff which best differentiated rhythm outcomes between RF-PVI and Cryo-PVI using a maximum likelihood approach based on the Cox proportional hazard model and investigated the relationship between PVI level and LA mass reduction through computational modeling. Results During the 24 months of median follow-up, Cryo-PVI showed poorer rhythm outcomes to RF-PVI (Log-rank p=0.009) in overall patients. However, Cryo-PVI showed comparable overall rhythm outcomes to RF-PVI (Log-rank p=0.370) in patients with paroxysmal AF. Cryo-PVI showed higher AF recurrence in patients with larger LA size (LA diameter≥40mm; hazard ratio [HR] 1.55 [1.04-2.30]; log-rank p=0.030) or with persistent AF (log-rank p=0.001). In the computational modeling, PV antrum was likely to be covered by Cryo-PVI in patients with small LA, but not in those with large LA. Conclusions Cryo-PVI showed inferior rhythm outcomes than RF-PVI in patients with higher LA diameter or with persistent AF.