Abstract Background As treatment options for atrial fibrillation (AF) increase, more attention is focused on patients' experiences and quality of life (QoL). However, little is known about the factors associated with these outcomes. Methods The Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) is a disease-specific QoL tool for AF, with domain and summary scores ranging from 0 (the worst QoL) to 100. Using multivariable linear regression, we evaluated factors associated with baseline AFEQT Summary and Subscale Scores in ORBIT AF, a large, community-based AF registry. Independent associations were reported as coefficient estimates in scores and 95% confidence intervals (CI). Results Overall, AFEQT was assessed in 2007 AF outpatients from 99 sites. Median age (IQR) was 76 years (67–82) and 43% were female. The median AFEQT summary score was 82 (67–94). Female sex, younger age, new onset AF, higher heart rate, obstructive sleep apnea, symptomatic heart failure (HF), chronic obstructive pulmonary disease and coronary artery disease were all independently associated with reduced QoL. Female sex Estimate −7.03, 95% CI (−9.31, −4.75) and new onset versus permanent AF Estimate −7.44, 95% CI (−11.03, −3.84) were independently associated with increased symptoms. NYHA Class III or IV HF Estimate −14.44, 95% CI (−19.46, −8.76) and female sex Estimate −7.91, 95% CI (−9.95, −5.88) were most independently associated with impaired daily activities. Conclusions QoL in patients with AF varies widely and is associated with several patient factors. Understanding patient factors independently associated with worse QoL can be a foundation for tailoring treatment.