Older patients with atrial fibrillation (AF) are challenging to treat due to concomitant increased risk for both stroke and bleeding and the presence of an increasing number of comorbidities. Data from clinical trials, meta-analyses, and real-world evidence support the relative merits of NOAC therapy compared with conventional anticoagulation in treating elderly patients with AF. This program focuses on the factors and considerations that can drive the choice of anticoagulation therapy for elderly patients with AF, such as comorbidities and associated medications, falling risk, and monitoring and treatment adherence, which may help clinicians optimize the care of their elderly patients with AF.