Introduction: Parameters used to gauge the effectiveness of a cryoballoon lesion have been described that monitor the ablation at the time of balloon-to-pulmonary vein (PV) occlusion, during the cryoablation freeze, and at the thaw phase of the cryoablation. This study examines the balloon-to-PV occlusion step and monitors the completeness of occlusion using capnography to measure end-tidal CO2 (ETCO2). Specifically, the main objective was to determine if ETCO2 measurements can be used to quantify the amount of balloon-to-PV occlusion and to determine if acute ETCO2 parameters could predict long-term freedom from atrial fibrillation (AF). Methods and Results: In a prospective study, 30 subjects were cryoballoon ablated for drug refractory symptomatic paroxysmal AF by pulmonary vein isolation method. During the balloon-to-PV occlusion and throughout the cryoablation, ETCO2 measurements were recorded. The subjects were followed for a 12-month period to monitor their freedom from AF. Five subjects had a recurrence of AF outside of a 90-day blanking period but before the 12-month endpoint. Between the 25 subjects that maintained normal sinus rhythm (NSR) and the 5 subjects that had recurrent AF (rAF), there were no statistical differences in procedural parameters, including: the number of cryoablations per PV, duration of each cryoablation, balloon nadir temperature, or balloon thaw time. Additionally, there were no statistical differences in baseline ETCO2 and in nadir ETCO2 between the two cohorts; however, when examining Δ ETCO2, the subjects in the NSR cohort had a significantly larger change compared to the rAF cohort (P<0.001). The largest change in ETCO2 during balloon-to-PV occlusion was observed during the cryoballoon ablation of the superior PVs; however, Δ ETCO2 did not solely predict long-term freedom from AF for the individual subject. Conclusions: Δ ETCO2 did tend to be larger in the NSR cohort compared to the rAF cohort; however, ETCO2 monitoring was more responsive in the superior PVs and less useful in the inferior PVs. Moreover, ETCO2 monitoring could not be used as a sole indicator of long-term efficacy. Suggesting that monitoring balloon-to-PV occlusion is a necessary first in cryoballoon ablation, but other parameters must be incorporated and observed as surrogates of a circumferential and transmural lesion formation with long-term durability.