Abstract Background Many atrial fibrillation (AF) patients have concomitant vascular diseases, and therefore, antithrombotic therapy is crucial for prevention of cardiovascular events in AF patients. In the last decade, antithrombotic therapy of AF patients has undergone major change due to launch of direct oral anticoagulants (DOAC). After the release of DOAC, several national guidelines for the management of AF were updated. The Japanese Circulation Society published the new guideline for the management of AF incorporating the recommendation of DOAC in 2014, which made a great impact on clinical practice in Japan. Purpose In this study, we investigated the year-to-year change of antithrombotic therapy of AF patients with vascular disease from 2011 to 2021 and compared the clinical characteristics and outcomes of those patients enrolled before and after the guideline (2011-2013 vs. 2014-2021) by using data of the Fushimi AF Registry. Methods The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. We started to enroll patients from March 2011 and follow up data including prescription status were available in 4,464 patients from March 2011 to August 2021. We defined vascular disease as coronary artery disease, peripheral artery disease, ischemic stroke or transient ischemic attack. Results In 2011, 61% of AF patients with vascular disease received OAC and 53% received antiplatelet drug (APD). Proportion of the patients receiving OAC increased year by year and that receiving APD decreased year by year. In 2021, 76% of the patients received OAC and 31% received APD. Proportion of the patients with combination of OAC and APD was 27% in 2011 and decreased year by year. In 2021, 18% received the combination therapy. In 2011, when the first DOAC was launched, 2% of the patients received DOAC and 59% received warfarin. After that, proportion of the patients receiving DOAC increased progressively. In 2021, 55% of patients received DOAC and 21% of patients received warfarin. Of 4,464 patients, 1,386 patients (31.0% of the entire cohort) had history of vascular disease at enrollment. Of 1,386 patients, 1,120 patients were enrolled before 2013 and 266 patients were enrolled after 2014. The incidence of composite of cardiac death, stroke or myocardial infarction was similar between the two groups (patients enrolled before 2013 vs. patients enrolled after 2014: 5.0 vs. 4.1 per 100 person-years; log-rank p=0.27). The incidence of major bleeding tended to be lower in patients enrolled after 2014 than those enrolled before 2013 although it was not statistically significant (2.8 vs. 2.0 per 100 person-years; log-rank p=0.15). Conclusion Antithrombotic strategy of AF patient with vascular disease has undergone major change in this decade, but the incidences of cardiovascular events of those patients have not significantly changed.