Introduction The objective of this study was to evaluate the cost-effectiveness of the treatment with cryoballoon (CB) compared to the standard treatment with traditional irrigated radiofrequency (RF) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation (pAF) refractory to antiarrhythmic drug therapy. Methods A decision tree model was developed to graphically depict the probabilities, utilities and costs of CB compared to RF therapy. Data from a conducted systematic literature review and meta-analysis of only RCTs were used to evaluate clinical outcomes of CB and RF treatments, including success rates after one year, complications and recurrence of atrial fibrillation. Results The cost-utility analysis estimated that, CB therapy had £1,747 higher cost, and 0.0114 more quality-adjusted life years (QALYs) compared to standard RF treatment over a one-year time horizon. The incremental cost per QALY of CB ablation compared to RF ablation was estimated to be £152,836/QALY. Conclusions Based on current evidence, CB ablation for pulmonary vein isolation in patients with pAF is costeffective compared to RF if decision makers are willing to pay £152,836 or higher for a QALY.