Purpose To date, clinical data on real-world treatment practices in Japanese patients with atrial fibrillation (AF) after bioprosthetic valve (BPV) replacement are needed. We conducted a large-scale, prospective, multicenter study to understand the actual usage of antithrombotic therapy and the incidence of thromboembolic and bleeding events in these patients, and to eliminate the clinical data gap between Japan and Western countries. Methods This was an observational study, in patients who had undergone BPV replacement and had a confirmed diagnosis of AF, with no mandated interventions. We report the baseline demographic and clinical data for the 899 evaluable patients at the end of the enrollment period. Results Overall, 45.7% of patients were male; the mean age was 80.3 years; AF was paroxysmal, persistent, or permanent in 36.9%, 34.6%, and 28.5% of patients, respectively. Mean risk scores for stroke and bleeding were 2.5 (CHADS2), 4.1 (CHA2DS2-VASc), and 2.5 (HAS-BLED). Many patients (76.2%) had comorbid hypertension and 54.8% had heart failure. Most BPVs (65.5%) were positioned in the aortic valve. Warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, and antiplatelet therapy (without warfarin and DOAC) were administered to 55.0%, 29.3%, and 9.7% of patients, respectively. Conclusion Patients enrolled into this study are typical of the wider Japanese AF/BPV population in terms of age and clinical history. Future data accruing from the observational period will contribute to future treatment recommendations and guide therapeutic decisions in patients with BPV and AF. Trial registration ClinicalTrials.gov Identifier: UMIN000034485 Electronic supplementary material The online version of this article (10.1007/s10557-020-07038-1) contains supplementary material, which is available to authorized users.