Objective: Background: Case Report: Conclusions: Unusual or unexpected effect of treatment Pulmonary vein isolation (PVI) is an effective treatment strategy for patients with paroxysmal atrial fibrillation (AF), yet it is associated with limited success rates in patients with persistent AF (PersAF). The left atrial appendage (LAA) was recently identified as a target of catheter ablation especially in PVI non-responders and LAA-isolation (LAAI) by cryoballoon or radiofrequency was shown to be effective. Recently the fourth-generation cryoballoon (CB4) was introduced to clinical practice. Here we are demonstrating the first case report of CB4-based LAAI followed by LAA-closure in a patient with PersAF. A 67-year-old male patient presented with symptomatic PersAF and thromboembolism due to LAA-thrombus. After resolving the LAA-thrombus cryoballoon based PVI and empirical LAAI was successfully performed. To prevent further thromboembolism LAA-closure was successfully performed after 6 weeks. On short-term follow-up (12 weeks) the patients stayed in stable sinus rhythm. Fourth-generation cryoballoon based ablation seems to be an effective treatment strategy for LAAI.