Introduction: Pulmonary vein (PV) isolation (PVI) with a balloon-based visually guided laser ablation (VGLA) is a useful tool for treating atrial fibrillation (AF), however, phrenic nerve injury (PNI) is an important complication. We investigated the predictors of developing PNI during VGLA. Methods and Results: This study included 130 consecutive patients who underwent an initial VGLA of non-valvular paroxysmal AF. During the ablation of the right-sided pulmonary veins, continuous and stable right phrenic nerve pacing was performed, and the compound motor action potentials (CMAPs) were recorded. Twenty patients developed PNI during the PVI. The patients who suffered from PNI had a significantly larger right superior PV (RSPV) ostium area (284.7 ± 47.0 mm2 vs. 233.1 ± 46.4 mm2, P < 0.01) than that of the other patients. Receiver operating characteristic analyses revealed that the area under the curve of the RSPV ostial area was 0.79 (95% confidence interval: 0.69-0.90) with an optimal cutoff point of 238.0 mm2 (sensitivity: 0.58, specificity: 0.95). In the multivariate analyses, large RSPV ostial area (HR 1.02, 95% confidence interval: 1.01-1.03, P < 0.01) and small balloon size (HR 0.72, 95% confidence interval: 0.53-0.98, P = 0.03) were independent risk factors for PNI. PNI remained in 13 patients after the procedure, but 12 of those patients recovered from PNI during the follow-up period. Conclusion: The incidence of PNI during the VGLA was relatively high, but the PNI improved in the majority of cases. During the VGLA, a large RSPV and small balloon size were predictors of PNI.