Background: Heart failure with preserved ejection (HFpEF) represents nearly half of all patients with heart failure (HF). The objective of this study was to examine the characteristics of patients with atrial fibrillation (AF) and HFpEF to determine factors that might explain the adverse prognosis. Methods and Results: Data were collected on 196 patients with HFpEF in a non-hospitalized setting. Clinical and laboratory variables were collected. Patients with AF were compared to those with sinus rhythm. AF was present in 25% of the study population. Individuals with AF had a significant (p<0.05) and three-fold greater B-type natriuretic peptide level than individuals without AF. Individuals with AF had significantly (p<0.05) larger left atrial volumes. AF was associated with evidence of significantly (p<0.05) worse diastolic function and was also significantly greater prevalence of moderate mitral or tricuspid regurgitation. In multivariate analysis, considering age, left atrial volume index, E/A ratio, E/e’ and left ventricular internal diameter (LVID), only age and left atrial volume index were significant (p<0.05) independent factors related to the presence of atrial fibrillation in HFpEF. Conclusions: AF in patients with HFpEF is an indication of more severe or advanced heart failure. Several explanations are possible as unifying cellular pathways that links atrial fibrillation and HFpEF specifically processes leading to increases in atrial and ventricular inflammation and/or fibrosis.