Background: The CRYO-Japan PMS study indicated that cryoballoon ablation (Cryo-Abl) has a lower acute success rate of pulmonary vein isolation (PVI) for the right and left inferior PVs (RIPV and LIPV, respectively) than for the superior PVs. This study aimed to determine if the orientation and position of the inferior PVs are related to the difficulty of acute success of PVI. Methods and Results: We investigated 30 consecutive patients who underwent Cryo-Abl. A "difficult PV" was defined as the requirement for >2 cooling applications and/or touch-up ablation to achieve PVI. We measured the ventral angle between the vertical line and the direction of each PV trunk (PV angle) on the transverse plane of enhanced CT images. PV position was defined as the difference in the levels between the bottom of the RIPVs and the non-coronary cusp of the aorta. PV angle <105 and PV position <1.250 mm were independent factors of difficult RIPV isolation (PV angle: odds ratio (OR)=23.80, confidence interval (Cl) 3.15528 to -0.53622, P=0.002; PV position: OR=12.14, Cl -2.77301 to -0.23160, P=0.014). PV position <16.875mm was also related to the difficulty of LIPV isolation (OR=5.78, CI -1.77095 to -0.09474, P=0.027). Conclusions: RIPV with ventral orientation may require difficult maneuvers to advance an ablation system towards it. Low take-off of the inferior PVs may cause non-coaxial configuration of balloon catheters towards the direction of these veins.