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Background Diabetes mellitus has been a major concern as a common risk factor for cardiovascular disease. Glycated hemoglobin (HbA1c) variability is an indicator of long-term blood glucose fluctuation. Therefore, it is of great clinical significance to explore the correlation between HbA1c variability and new-onset atrial fibrillation (AF) in diabetic patients combined with heart failure with preserved ejection fraction (HFpEF) . Objective To investigate the correlation between HbA1c variability and new onset AF in type 2 diabetes mellitus (T2DM) patients combined with HFpEF. Methods The clinical data of 317 T2DM patients combined with HFpEF diagnosed in the Department of Cardiology, the Second Affiliated Hospital of Zhengzhou University from January 2018 to January 2019 were retrospectively analyzed. The follow-up was performed until February 2022, with a mean follow-up time of 3.4 years. The included patients were divided into the AF group (34 cases) and non-AF group (283 cases) based on the presence of new-onset AF during the follow-up period. The HbA1c variability was expressed as standard deviation of HbA1c measurement (HbA1c-SD) and HbA1c coefficient of variation (HbA1c-CV). Multivariate Cox regression analysis was used to explore the correlation between HbA1c variability and new-onset AF in T2DM patients combined with HFpEF. The survival curves were plotted by the Kaplan-Meier (K-M) method. The receiver operating characteristic (ROC) curve of HbA1c variability predicting new-onset AF in T2DM patients combined with HFpEF was plotted. Results The HbA1c-SD and HbA1c-CV of patients in the AF group were higher than those in the non-AF group (P0.34%, HbA1c-CV>4.74%) groups according to the median of HbA1c variability. Log-rank test results showed higher incidence of new-onset AF in patients with high HbA1c variability (PHbA1c-SD0.34%, HbA1c-CV>4.74%) is independently associated with an increased risk of new-onset AF in T2DM patients combined with HFpEF, with significant clinical value in predicting AF.