A left common pulmonary vein (LCPV) accounts for the most frequent PV variation. Use of the cryoballoon (CB) for isolating these veins is still debatable. To date, no data are available regarding the feasibility, acute PV isolation, and clinical outcome of the second-generation CB (CB-A) in this setting. The purpose of this study was to investigate the performance of the CB-A in patients with LCPVs. In a total cohort of 433 patients having undergone CB-A ablation for drug-refractory atrial fibrillation together with preprocedural computed tomographic scanning, 146 patients presented an LCPV. Measurement of ostial area and trunk distance was performed, together with analysis of procedural and fluoroscopic data in order to determine the ablation strategy. The latter 146 LCPV+ patients were compared for outcome with a cohort of 146 propensity-score matched LCPV- patients. Electrical isolation could be achieved in all left-sided veins. A long left common trunk (>15 mm) was found in 25% (37/146) of the LCPV+ patients. LCPVs treated with a single-shot freeze strategy presented a longer trunk (22 ± 5 mm vs 9 ± 4 mm, P<.001) and smaller ostial area (305 ± 109 mm2 vs 400 ± 108 mm2, P <.001) compared to LCPV patients in whom a segmental (superior and inferior) freeze was delivered. Survival free from atrial fibrillation was similar between LCPV+ and LCPV- patients during mean follow-up of 19 ± 10 months (log rank P = .33). CB-A ablation in LCPV+ patients is effective and showed no difference in clinical outcome compared to LCPV- patients.