BACKGROUND In patients with non-valvular atrial fibrillation (NVAF), intracranial bleeding (ICB) constitutes a very challenging situation in which the rate of both ischemic and hemorrhagic events is increased. In these patients, left atrial appendage occlusion (LAAO) might represent a very valid alternative. OBJECTIVES To investigate the procedural safety and long-term outcome of patients undergoing LAAO therapy due to previous ICB. METHODS Data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients were analyzed. Patients with previous ICB as indication for LAAO were compared to patients with other indications. RESULTS A total of 198 patients (18.9%) with previous ICB were identified. The CHADS-VASc score was similar (4.5±1.5 vs. 4.4±1.6, p=0.687) and the HAS-BLED score was higher in patients with previous ICB compared to those without (3.5±1.1 vs. 3.1±1.2, p<0.001). No significant differences in peri-procedural major adverse events were observed (2.5 vs 5.4%, p=0.1). Patients with previous ICB were more frequently on single acetylsalicylic acid therapy after LAAO (42.4% vs. 28.3%; p<0.001). With an average follow-up of 1.3years, the observed annual stroke/TIA rate (procedure and follow-up) for patients with previous ICB was 1.4% (75% relative risk reduction). The observed annual major bleeding rate (procedure and follow-up) for patients with previous ICB was 0.7% (89% relative risk reduction). CONCLUSIONS In patients with NVAF and previous ICB, LAAO seemed to be a safe procedure and was associated with a significant reduction in stroke/TIA and a remarkably low frequency of major bleeding during follow-up.