Background Oral anticoagulation (OAC) with vitamin K antagonist is increasingly being used for the prevention of venous thromboembolism and stroke in atrial fibrillation (AF). Bleeding is the major concern for OAC, especially in patients with history of ulcer. We evaluated the safety and efficacy to prevent thromboembolism of OAC in AF patients with the history of ulcer. Methods The study included 430 AF patients with healed ulcer. We compared composite end points including major adverse cardiac events (MACE) and major bleeding between patients with OAC (Group 1, n=200) and without OAC (Group 2, n=230). MACE included stroke, myocardial infarction, pulmonary thromboembolism and other systemic embolism. Results Patients in group 1 was younger than those in group 2 (67.3짹9.7 vs. 69.7짹10.4 years, p=0.01). Antiplatelet agents was prescribed in 69 (35%) group 1 and 112 (49%) group 2 patients (p=0.001). During the follow up period of 3.3짹2.7 years, 46 (23%) and 25 (11%) patients had major bleeding in group 1 and 2, respectively (p=0.001). Among the bleeding sites, ulcer bleeding was more common in group 1 than 2 (16% vs 9%, p=0.03). While 25 (13%) group 1 patients had experienced MACE, 62 (27%) group 2 patients had MACE (p=0.001). During follow up period, 11(6%) and 6 (3%) patients experienced both major bleeding and MACE in group 1 and 2, respectively (p=0.008). There was no significant difference in composite end points between group 1 and 2 (29% vs. 36%, p=0.08). However, group 1 patients who achieved time in therapeutic range ���60% in INR 1.5~3.0 showed better cumulative survival free from composite end points than group 2 (p=0.02). These patients also had decreased hazard ratio of MACE or major bleeding (relative risk 0.52; 95% CI 0.32 ~ 0.84, p=0.007). Conclusion The OAC treatment in AF patients with healed ulcer deceased MACE and increased major bleeding simultaneously, making no difference in in composite end point. However, patients with OAC who were constantly maintained in optimal INR level showed better composite endpoint than those without OAC because of the reduction of MACE.