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To date, multiple modes of research have been leveraged to study the optimal cryoballoon ablation parameters to safely, effectively and efficiently isolate the pulmonary veins for the treatment of atrial fibrillation. Basic scientific investigation, pre-clinical studies, clinical observations, trials and more recently computational modelling have helped to generate and test new hypotheses for the advancement of cryoballoon treatment in patients with atrial fibrillation. In this review, we examine the data and evidence that have contribu