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Aims Cryoballoon pulmonary vein isolation (CB-PVI) offers similar efficacy to point-by-point radiofrequency PVI for patients with atrial fibrillation (AF), but generally with higher X-ray exposure. Strategies aimed at reducing fluoroscopy mostly rely on other costly imaging techniques, limiting their applicability. We designed a Systematic Workflow and Electrogram guidance to reduce X-ray Exposure Time during CB-PVI (SWEET-Cryo) strategy and analysed its impact on fluoroscopy use and acute procedural and clinical outcomes. Methods and results We enrolled 100 patients with paroxysmal or persistent AF undergoing CB-PVI by two operators with different levels of expertise. Patients treated with the SWEET-Cryo strategy (prospective cohort; n = 50) or conventional fluoroscopy (retrospective control cohort; n = 50) were compared. When applied by the senior operator, the SWEET-Cryo strategy significantly reduced the mean fluoroscopy time (FT) (2.6 ± 1.25 vs. 20.3 ± 10.8 min) and mean dose area product (DAP) (5.1 ± 3.8 vs. 35.3 ± 22.3 Gy cm2) compared with those of the control group, respectively (P < 0.001). Significant reductions in FT (6.4 ± 2.5 min vs. 32.5 ± 10.05) and DAP (13.9 ± 7.7 vs. 92.3 ± 63.8) were also achieved by the less experienced operator (P < 0.001). No difference was observed in acute and long-term complications or freedom from AF between fluoroscopy strategies during a 33-month median follow-up. Mean FT was maintained below 3 min in randomly selected cases performed during the follow-up period. Conclusion In contrast to conventional protocols and regardless of the operator's experience, the optimized SWEET-Cryo strategy dramatically reduced fluoroscopy exposure during CB-PVI. The efficacy, safety, or added costs of the ablation procedure were not compromised. [ABSTRACT FROM AUTHOR]