Second-Generation Cryoballoon versus RF. Introduction:There are limited comparative data on catheter ablation of atrial fibrillation (CAAF) using the second-generation cryoballoon (CB-2) versus point-by-point radiofrequency (RF). This study examines the acute/long-term CAAF outcomes using these 2 strategies.Methods and Results: In this multicenter, retrospective, nonrandomized analysis, procedural and clinical outcomes of 1,196 patients (76% with paroxysmal AF) undergoing CAAF using CB-2 (n = 773) and openirrigated, non-force sensing RF (n = 423) were evaluated. Pulmonary vein isolation was achieved in 98% with CB-2 and 99% with RF (P = 0.168). CB-2 was associated with shorter ablation time (40 ± 14 min vs. 66 ± 26 min; P < 0.001) and procedure time (145 ± 49 minutes vs. 188 ± 42 minutes; P < 0.001), but greater fluoroscopic utilization (29 ± 13 minutes vs. 23 ± 14 minutes; P < 0.001). While transient (7.6% vs. 0%; P < 0.001) and persistent (1.2% vs. 0%; P = 0.026) phrenic nerve palsy occurred exclusively with CB-2, other adverse event rates were similar between CB-2 (1.6%) and RF (2.6%); P = 0.207. However, freedom from AF/atrial flutter/tachycardia at 12 months following a single procedure without antiarrhythmic therapy was greater with CB-2 (76.6%) versus RF (60.4%); P < 0.001. While this difference was evident in patients with paroxysmal AF (P < 0.001), it did not reach significance in those with persistent AF (P = 0.089). Additionally, CB-2 was associated with reduced long-term need for antiarrhythmic therapy (16.7% vs. 22.0%; P = 0.024) and repeat ablations (14.6% vs. 24.1%; P < 0.001).Conclusion: In this multicenter, retrospective, nonrandomized study, CAAF using CB-2 coupled with RF as occasionally required was associated with greater freedom from atrial arrhythmias at 12 months following a single procedure without antiarrhythmic therapy when compared to open-irrigated, non-force sensing RF, alone. (J Cardiovasc Electrophysiol, Vol. 26, pp. 832-839, August 2015) atrial fibrillation, catheter ablation, cryoablation, cryoballoon, phrenic nerve palsy Drs. Aryana, Kowalski, Banker, and O'Neill have received consulting fees and speaker honoraria, and Drs. Aryana and O'Neill have received a research grant from Medtronic, Inc., the manufacturer of the second-generation cryoballoon used in this study. Additionally, Drs. Cohen, Banker, Fuenzalida, and d'Avila have received consulting fees and speaker honoraria, and Drs. Aryana and O'Neill have received research grants from Biosense Webster, Inc., the manufacturer of the radiofrequency ablation catheter used in this study. Other authors: No disclosures.