Background: Cryoballoon (CB)-based pulmonary vein isolation (PVI) is an established treatment modality for patients suffering from paroxysmal or persistent atrial fibrillation (AF). Recently, the novel fourth-generation cryoballoon (CB4) was introduced which mainly provides a 40% shorter distal tip as compared to the second-generation cryoballoon (CB2). This two-centre analysis sought to assess the primary efficacy of the 28 mm CB4 for PVI and the feasibility of real-time signal recordings from the PVs considering the time-to-isolation (TTI).Methods and results: Eighty-four patients with paroxysmal or short-standing persistent AF underwent CB4-based PVI at two different hospitals. Individual freeze-cycle duration was set at TTI + 120 seconds. No bonus freeze was applied. A total of 331 pulmonary veins (PVs) including five left common PVs were identified and all PVs were successfully isolated. Mean freeze-cycle duration was 165.7 ± 31.5 seconds. The mean minimal CB temperature was -45.6 ± 7.6 °C with a real-time PVI visualisation rate of 78% (67/84 (79.8%) RSPVs, 55/84 (65.5%) RIPVs, 67/79 (84.8%) LSPVs, 66/79 (83.5%) LIPVs and 2/5 (40%) LCPV). Transient phrenic nerve palsy occurred in 2/84 (2.4%) patients during cryo-application along the RSPV.Conclusions: The novel CB4 provides both, a high acute efficacy and a high rate of real time electrical PV-recordings, thus facilitating individual ablation strategies based on TTI.