Abstract Background Atrial fibrillation (AF) is known as a common arrhythmia in heart failure patients with preserved left ventricular ejection fraction (HFpEF). Several studies have reported that HFpEF patients with AF show lower exercise tolerance and poorer prognosis as compared with those with sinus rhythm (SR). On the other hand, exercise training is documented to improve peripheral muscle function and exercise tolerance in HFpEF patients. However, the relationship between AF status and outcomes due to exercise training is still unclear in these patients. Purpose We aimed to investigate the influence of AF on the responses to outcomes with exercise training in HFpEF patients. Methods We studied 426 patients with HFpEF who received 5-month cardiac rehabilitation including exercise training during hospitalization and after hospital discharge. As clinical characteristics, we obtained body mass index, disease aetiology, comorbidity conditions, blood examination and echocardiographic variables from medical records. We also measured isometric quadriceps strength (QS) and 6-minute walk distance (6MWD) as peripheral muscle strength and exercise tolerance, respectively. The QS and 6MWD were assessed at hospital discharge as the baseline and 5 months later. AF status was determined by the presence on electrocardiogram at baseline 6MWD or medical history of AF during hospitalization. In statistical analysis, we compared baseline clinical characteristics, QS and 6MWD between the rhythm status (SR group or AF group). We also examined the changes in QS and 6MWD from baseline to the 5-month observation period (ΔQS and Δ6MWD) and compared them between the 2 groups using analysis of covariance with adjustment for baseline clinical confounding factors. Results At baseline, 289 patients (68%) were in SR, and 111 patients (26%) had AF. The AF was associated significantly with older age (P<0.001) and lower levels of estimated glomerular filtration rate (P=0.013), QS (P<0.001) and 6MWD (P<0.001) at baseline. The QS increased significantly from 25.2±11.0 kg at baseline to 30.8±13.0 kg after 5-month cardiac rehabilitation in the SR group, and from 21.1±8.3 kg to 26.0±9.4 kg in the AF group (P<0.001, respectively). The 6MWD also increased significantly from 394.8±129.2 to 463.5±133.5 meters in the SR, and from 343.7±107.9 to 403.0±114.5 meters in the AF (P<0.001, respectively). There were no significant differences in ΔQS and Δ6MWD between the SR and AF groups even after adjustment for clinical confounding factors including baseline QS or 6MWD (Figure). Conclusions The AF status in HFpEF patients was associated with older age, lower peripheral muscle function and also lower exercise tolerance at baseline, but not associated with the responses to exercise training. Acknowledgement/Funding JSPS KAKENHI JP16K16442