Abstract Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the ORBIT-AF II registry, we analyzed rates of ISTH major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total 344 AF patients experienced major bleeding events over a median follow-up of 360 days follow-up: n=273 on NOAC (3.3 per 100 patient-years) and n=71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p=0.5), as was GI bleeding (1.8 for NOAC vs. 1.3 for warfarin, p=0.1). Blood products and correction agents were less-commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs. 76%, p=0.0004 for blood products; 0% vs. 1.5% for recombinant factor; p=0.0499); no patients received pharmacological hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 (8.4%) NOAC-treated patients died versus 5 (7.0%) on warfarin (p=0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement.