Abstract Introduction Atrial fibrillation (AF) frequently accompanies heart failure with preserved ejection fraction (HFpEF). AF exacerbates HFpEF through adverse haemodynamic effects. In turn, HFpEF promotes AF through adverse left atrial remodelling. Observational data suggest sinus rhythm restoration improves outcomes in patients with AF and HFpEF. However, there are no randomised data examining the effects of rhythm control with catheter-based AF ablation on HFpEF outcomes. Purpose To compare the effects of AF ablation versus usual medical therapy on markers of HFpEF severity, including exercise haemodynamics, natriuretic peptide levels and patient symptoms. Methods Patients with symptomatic AF and HFpEF underwent exercise right heart catheterization (RHC) and cardiopulmonary exercise testing (CPET). HFpEF diagnosis was based on left ventricular ejection fraction (LVEF) ≥50%, elevated natriuretic peptide and echocardiographic diastolic impairment. HFpEF was confirmed on exercise RHC based on peak exercise pulmonary capillary wedge pressure (PCWP) of ≥25mmHg. Patients were randomised to AF ablation versus medical therapy, with investigations repeated at 6 months. The primary outcome was change in PCWP on follow-up. Results 31 patients aged 66.1±7.5 years were randomized to AF ablation (16) versus medical therapy (15), with 51.6% female and 80.6% persistent AF. Baseline characteristics were comparable across groups. Paired analyses of ablation cohort showed significant reductions in peak PCWP (29.6±3.7 vs 25.9±4.6 mmHg, p<0.01), PCWP indexed for workload (39.0±57.9 vs 33.0±50.5 mmHg/W/kg, p<0.01), and BNP (146.2±80.5 vs 82.2±75.4 pg/mL, p=0.01); and increased resting cardiac output (4.6±0.9 vs 5.6±1.2 L/min, p=0.01), peak cardiac output (9.6±4.2 vs 10.4±3.7 L/min, p=0.02), peak (30s averaged) VO2 (1875.1±759.2 vs 2193.7±878.1 mL/min, p<0.01), peak absolute VO2 (1937.3±739.3 vs 2216.3±861.9 mL/min, p<0.01), peak (30s averaged) relative VO2 (19.4±5.9 vs 22.9±7.4 ml/kg/min) and peak workload (162.0±81.1 vs 184.4±83.4 W, p<0.01). Quality of life scores improved: AFEQT (45.3±20.9 vs 75±20.7, p<0.01) and MLHF (53±23.3 vs 17.5±22.8, p<0.01). Reversal of HFpEF by PCWP criteria occurred in 31.2% following AF ablation, and 50% among those free from arrhythmia recurrence. In the medical arm, there were no significant differences in RHC, CPET, and natriuretic peptide outcomes on follow-up versus baseline. Repeated measures mixed ANOVA testing showed significant time-randomisation interaction on peak VO2, absolute peak VO2, peak relative VO2, AFEQT/ MLHF scores, suggesting that significant improvements in these parameters were related to AF ablation. Conclusion In patients with concomitant AF and HFpEF, AF ablation improves invasive exercise haemodynamic parameters, increases exercise capacity, and enhances quality of life. Successful AF ablation may reverse the clinical syndrome of HFpEF in a subset of cases. Funding Acknowledgement Type of funding sources: None.