Background: Simultaneous atrial fibrillation (AF) catheter ablation and left atrial appendage closure (LAAC) is sometimes recommended for both rhythm control and stroke prevention. However, the advantages of intracardiac echocardiography (ICE) guidance for this combined procedure have been scarcely reported. To evaluate the clinical outcomes and safety of ICE guided LAAC within a zero-fluoroscopy catheter ablation procedure. Methods and Results:From April 2019 to April 2020, 56 patients with symptomatic AF underwent concomitant catheter ablation and LAAC. ICE with a multi-angled imaging protocol mimicking the TEE echo windows was used to guide LAAC. Successful radiofrequency catheter ablation and LAAC was achieved in all patients. Procedure-related adverse event rate was 3.6%. During the 12-month follow-up, 77.8% of patients became free of arrhythmia recurrences and oral anticoagulants were discontinued in 96.4% of patients. No ischemic stroke occurred despite two cases of device-related thrombosis versus an expected stroke rate of 4.8% based on the CHA2DS2-VASc score. The overall major bleeding events rate was 1.8%, which represented a relative reduction of 68% versus an expected bleeding rate of 5.7% based on the HAS-BLED score of the patient cohort. The incidence of iatrogenic atrial septal defect secondary to a single transseptal access dropped from 57.9% at 2 months to 4.2% at 12 months TEE follow-up. Conclusion:The combination of catheter ablation and LAAC under ICE guidance was safe and effective in AF patients with high stroke risk. ICE with our novel protocol was technically feasible for comprehensive and systematic assessment of device implantation.