Pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) is a well-established method for the treatment of atrial fibrillation (AF). As a rule, cryoenergy delivery is preceded by demonstrating full pulmonary vein (PV) occlusion by injecting contrast. Research on CBA without the use of contrast is sparse. The aim of the study was to determine efficacy and safety of a simplified protocol for CBA performed without demonstrating PV occlusion by venography and compare achieved results with those observed in patients undergoing conventional CBA. Methods This was a dual-centre, prospective, nonrandomized study (NCT04344743). The study cohort consisted of consecutive patients with paroxysmal AF, with 4 separate pulmonary veins (PVs), undergoing a first-time CBA. All ablations were performed using a 28-mm cryoballoon catheter (Arctic Front Advance, Medtronic). In the non-contrast (NC) group CBA was performed using standardized protocol without demonstrating PV occlusion by venography prior cryoapplication. In the case of PV isolation failure after a total of 5 minutes of cryoenergy delivery further attempts to isolate the vein were preceded by venography. A similar protocol was used in the conventional contrast (CC) group, where ablations were performed after confirmation of complete vein occlusion by venography. In both groups PVI was confirmed by demonstrating entrance and exit block using a diagnostic circular catheter (Achieve, Medtronic). Results The NC and CC groups comprised 51 and 22 patients, respectively. There were no differences between the NC and CC groups regarding baseline demographic, clinical and echocardiographic data. In the NC group 184 (90%) out of 204 veins were isolated without previous venography. Isolation of all 4 PVs without venography was possible in 34 (67%) patients. There were no differences between the NC and CC groups in terms of procedure duration (89.7 ± 22.6 vs. 90.0 ± 20.6 min; p=0.7) , left atrium dwelling time (71.2 ±21.3 vs 69.9 ± 19.1 min; p=0.8), fluoroscopy time (15.3 ± 6.3 vs. 15 ± 4.5 min; p=0.8) and radiation dose exposure (815 ± 594 vs. 945 ± 529 cGy*cm ²). In the NC group, the use of contrast was significantly lower compared to the CC group (4.9 ± 10.1 vs. 19.4 ± 8.6 ml, p<0.001). The time to isolation and the minimum temperature achieved were comparable between the NC and CC groups. There were no serious adverse events in both groups. A one year freedom from AF was achieved in 73.5% and 71.5% of patients from the NC group the CC group, respectively (p=1). Conclusions Cryoballoon ablation without demonstrating vein occlusion with contrast is feasible, safe and enables isolation of the vast majority of pulmonary veins. The acute and one-year results for non-contrast cryoballoon ablation are comparable to those obtained using the conventional protocol with contrast.