Abstract Introduction Pulmonary vein isolation (PVI) represents the cornerstone of catheter ablation procedures in patients with symptomatic paroxysmal/persistent atrial fibrillation (AF). Conventionally, PVI is performed using fluoroscopy, but it can also be performed using the zero-fluoroscopy (ZF) technique with the assistance of electroanatomical mapping systems and intracardiac ultrasound, achieving fluoroscopy-free procedures. Purpose Our study aimed to compare procedural data of ablation-index guided point-by-point radiofrequency (RF) PVI performed with non-zero-fluoroscopy (NZF) vs. ZF approaches. Methods We enrolled 100 consecutive patients undergoing PVI for antiarrhythmic drug- refractory AF in our prospective observational study. In the first 50 cases, PVI was performed using the NZF technique, and in the other 50 cases, the ZF technique was applied. Procedural time, fluoroscopy exposure, ablation parameters, and the occurrence of complications were compared between the two groups. Results Compared to the NZF group, procedural time (59.6±10.7 min vs. 74.6±13.2 min, p<0.0001) was significantly shorter in the ZF group. This difference was mainly driven by the time from puncture to the beginning of left atrial mapping, which was significantly longer in the NZF group (17 [16; 20] min vs. 31 [23; 34.5] min, p<0.001). No differences were found between the two approaches in the number of RF applications (81 [73; 103] vs. 83 [71; 91], p=0.67), total ablation energy (54986 ± 13093 Ws vs. 55500 ± 11907 Ws, p=0.48), and the left atrial dwelling time (41.5 [36; 52.5] min vs. 40.5 [35; 46], p=0.14). No complications occurred in either group. In the ZF group, complete elimination of fluoroscopy was achieved in all cases, resulting in significant differences in fluoroscopy time (0 [0; 0] sec vs. 132 [100; 160] sec, p<0.0001] and dose (0 [0; 0] mGy vs. 4.8 [4.1; 8.2] mGy, p<0.0001) compared to the NZF technique. The acute success rate was 100% in the study population, and no complications occurred during the study period. Conclusion Ablation-index guided ZF PVI is feasible and safe. Using this technique, the procedure time can be shortened besides achieving a similar acute success rate without increasing complications.