ABSTRACT: Atrial fibrillation (AF) is associated with an increased risk for adverse events in patients with heart failure with preserved ejection fraction (HFpEF), but it is currently unknown if gender differences in these outcomes exist. To explore this hypothesis, we examined gender differences in the associations of AF with adverse outcomes in 3,385 (mean age 69 ± 9.6 years, 49% male, 89% white) patients with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial. Baseline AF cases were identified by self-reported history, medical record review, and baseline electrocardiogram data. Outcomes were adjudicated by a clinical end point committee and included the following: hospitalization, hospitalization for heart failure, stroke, death, and cardiovascular death. Cox regression was used to examine the risk of each outcome associated with AF. Over a median follow-up of 3.4 years, AF was associated with an increased risk for hospitalization (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.34 to 1.66), hospitalization for heart failure (HR 1.49, 95% CI 1.23 to 1.81), stroke (HR 2.10, 95% CI 1.43 to 2.09), death (HR 1.22, 95% CI 1.02 to 1.47), and cardiovascular death (HR 1.31, 95% CI 1.04 to 1.65). The association between AF and hospitalization was stronger in women (HR 1.63, 95% CI 1.40 to 1.91) than men (HR 1.37, 95% CI 1.18 to 1.58; p-interaction = 0.032). Although significant interactions were not observed for the other outcomes, we appreciated that the risk estimates were higher for women compared with men. In conclusion, AF increases the risk for adverse cardiovascular outcomes in patients with HFpEF, and the presence of this arrhythmia in women possibly is associated with a greater risk for adverse events than men.