Background Among older patients with atrial fibrillation, there are limited data examining clinically meaningful changes in quality of life (QoL). We examined the extent of, and factors associated with, clinically meaningful change in QoL over 1-year among older adults with atrial fibrillation. Methods and Results Patients from cardiology, electrophysiology, and primary care clinics in Massachusetts and Georgia were enrolled in a cohort study (2015-2018). The Atrial Fibrillation Effect on Quality-of-Life questionnaire was used to assess overall QoL and across 3 subscales: symptoms, daily activities, and treatment concern. Clinically meaningful change in QoL (ie, difference between 1-year and baseline QoL score) was categorized as either a decline (≤-5.0 points), no clinically meaningful change (-5.0 to +5.0 points), or an increase (≥+5.0 points). Ordinal logistic models were used to examine factors associated with QoL changes. Participants (n=1097) were on average 75 years old, 48% were women, and 87% White. Approximately 40% experienced a clinically meaningful increase in QoL and 1 in every 5 patients experienced a decline in QoL. After multivariable adjustment, women, non-Whites, those who reported depressive and anxiety symptoms, fair/poor self-rated health, low social support, heart failure, or diabetes mellitus experienced clinically meaningful declines in QoL. Conclusions These findings provide insights to the magnitude of, and factors associated with, clinically meaningful change in QoL among older patients with atrial fibrillation. Assessment of comorbidities and psychosocial factors may help identify patients at high risk for declining QoL and those who require additional surveillance to maximize important clinical and patient-centered outcomes.