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Background: The clinical performance of high-power, short-duration (HPSD) pulmonary vein isolation (PVI) with the novel flexible tip TactiFlex™ (TFSE) catheter, as compared to standard-power, long-duration (SPLD) PVI using the TactiCath™ (TCSE) catheter among patients undergoing catheter ablation (CA) of atrial fibrillation (AF) is currently unknown., Methods: We conducted a prospective, observational, single-centre study including 40 consecutive patients undergoing PVI for paroxysmal/persistent AF, using HPSD ablation with the novel TFSE catheter (HPSD/TFSE group). Based on propensity score-matching, forty patients undergoing SPLD PVI with the TCSE catheter were identified (SPLD/TCSE group). In the HPSD/TFSE group, RF lesions were performed by delivering 40-50 W for 10-20 s, while in the SPLD/TCSE group, RF power was 30-35 W, targeting a lesion size index (LSI) of 4.0-5.5. The co-primary study outcomes were time required to complete PVI and first pass isolation (FPI)., Results: PVI was achieved in 100% of patients in both groups, and no major adverse events were observed. Remarkably, PVI time was shorter in the HPSD/TFSE, compared to the SPLD/TCSE group(9 [7-9] min vs. 50 [37-54] min; p < 0.001), while FPI rate was non-significantly higher in the former group(91% [146/160] vs 83% [134/160]; p = 0.063). Shorter procedural (108 [91-120] min vs. 173 [139-187] min, p < 0.001), total RF (9 [7-11] min vs. 43 [32-53] min, p < 0.001), fluoroscopy times(15 [10-19] min vs. 18 [13-26] min, p = 0.014), and lower DAP (1461 [860-2181] vs. 7200 [3400-20,800], p < 0.001) were recorded in the HPSD/TFSE group. A higher average impedance drop was obtained with HPSD/TFSE CA(17[17-18]Ω vs. 16 [15-17] Ω, p < 0.001)., Conclusions: In our initial clinical experience, HPSD PVI with the TFSE catheter proved faster than SPLD PVI with the TCSE catheter, at least equally effective in terms of FPI, and it was associated with greater impedance drop., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)