Abstract Introduction Pulsed Field Cryoablation (PFCA) is dual-energy cardiac ablation modality consisting of short-duration ultra-low temperature cryoablation (ULTC) followed immediately by pulsed electric field ablation (PFA) delivered from the same catheter. It has been hypothesized that it may be beneficial to combine the efficiency of PFA with the contact and stability offered by ULTC. In patients with persistent atrial fibrillation, PFCA could be of particular benefit when creating extended lesion sets beyond pulmonary vein isolation such as posterior wall ablation. By focusing the electric field in high-impedance frozen tissue, PFCA may increase lesion depth and durability despite lower delivered current, while minimizing PFA-related microbubbles and skeletal muscle contraction. Purpose To report the acute outcomes of PFCA observed in the first-in-human PARALELL trial. Methods PFCA was performed using a novel stylet-driven catheter connected to the dedicated ULTC and PFA energy sources. The protocol-defined lesion set included pulmonary vein isolation and posterior wall (PW) ablation, with additional left and right atrial targets per operator discretion. Circular and linear lesions of varying dimensions were created by in-vivo shaping of the flexible, 11 cm-long ablation element of the catheter using exchangeable stylets. The ULTC freeze of 30 second duration was followed immediately by bipolar, biphasic PFA pulse trains delivered sequentially between the pairs of sixteen 3-mm electrodes evenly spaced along the ablation element. Results At 5 European and Canadian sites, 26 patients (age 68±9 years, 88.5% male, median left atrial size 45 mm, IQR [43 mm-48 mm]) underwent PFCA with 22.6 ± 9.6 ablation lesions per patient. The lesion set included 11.9 ± 4.1 lesions to PVs, 7.4 ± 2.7 to the PW, and in 14 patients, 6.6 ± 9.0 lesions to other atrial targets (left atrial roof and floor, PV carinas, mitral and cavotricuspid isthmuses). Isolation was achieved in 94.2% (98 of 104) of PVs and 92.3% (24 of 26) of PWs. The average procedure time was 130.3 ± 40.9 minutes, with catheter dwell time of 78.8 ± 26.0 minutes. Procedure-related groin hematoma at discharge was the only serious adverse event by site adjudication. Intracardiac echocardiography (ICE) performed in 18 patients identified Grade I (FEW) microbubbles in 1.3% (5 of 398) of ablations. Similarly, only faint muscular contractions were observed in 2 of 26 patients, occurring during 1.2% (4 of 339) of lesions placed in 15 patients not receiving any paralytic agents. Conclusions This initial multi-center experience suggests that PFCA can be efficiently performed on multiple atrial targets using a single versatile catheter system, with high acute success and good early safety profile, including minimal occurrence of PFA-related microbubbles and skeletal muscle contractions. The evaluation of the chronic 12-month effectiveness vs ULTC benchmarks and PFA comparators is ongoing.