The purpose of this study was to quantify the relationship between a drop in end-tidal carbon dioxide (etCO2) and occlusion of pulmonary veins (PVs) to find a delta etCO2 (ΔetCO2) able to predict occlusion during PV isolation (PVI) by cryoballoon. We designed a prospective registry. Paroxysmal atrial fibrillation patients who underwent cryoballoon PVI were included. Capnography was performed. Occlusion was tested by injection. A comparison between ΔetCO2 and occlusion was performed. Eighteen subjects (138 injections) were included. A drop of >3.5 mmHg predicted occlusion of the PV (sensitivity, 80%; specificity, 86.7%). A ΔetCO2 of ≥3.5 mmHg during inflation of the cryoballoon in each PV directly correlates with PV balloon occlusion.