Background Radiofrequency and cryoballoon pulmonary vein isolation are common approaches for paroxysmal atrial fibrillation treatment, showing similar results in recent multicenter studies, including heterogeneous tools and protocols. The aim of this study is to compare prospectively in a single, high-volume center the outcome of paroxysmal atrial fibrillation ablation performed specifically by second-generation cryoballoon or contact force radiofrequency ablation. Methods Consecutive patients scheduled for paroxysmal atrial fibrillation transcatheter ablation have been included and prospectively followed up. Aiming to reduce potential bias deriving from baseline characteristics, a propensity score matching analysis has been performed to analyze safety and efficacy outcomes. Results Out of consecutive patients undergoing atrial fibrillation transcatheter ablation between January 2015 and December 2016, 46 patients approached by cryoablation were matched 1:1 by propensity score to a similar population treated by last-generation radiofrequency ablation. Freedom from atrial fibrillation after 12 months (76 vs. 78%, P=0.804) and incidence of complications (4 vs. 6%, P=0.168) did not differ between the two groups. Radiological exposure was higher for the cryoballoon group (11 vs. 4min, P<0.001), whereas procedural duration did not differ (P=0.174). Aiming to assess the potential impact of a learning curve in patients undergoing cryoablation, the first-third of patients (n=15) were compared with the remaining, reporting longer radiological exposure (P<0.001), but similar safety and efficacy. Conclusion In this propensity score analysis, last-generation cryoballoon and radiofrequency catheters for atrial fibrillation ablation present similar efficacy and safety. Cryoablation requires longer fluoroscopy exposure compared with radiofrequency, although this is reduced by increased experience.