Background Recent research reports that regional adiposity, notably epicardial and visceral fat, may serve a pivotal pathophysiologic role in heart failure with preserved ejection fraction (HFpEF). We aimed to describe the role of regional adiposity in predicting all-cause death in patients with HFpEF. Methods This was a prospective cohort study in patients with HFpEF, and the primary outcome of this study was all-cause mortality. Visceral fat area (VFA) was measured through the multifrequency bioelectrical impedance analyzer (BIA). The thickness of epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) was measured by echocardiography. Cox regression analysis was used to evaluate the predicted effect of the potential risk factors. Test for interaction was used to estimate whether the prognostic value of VFA was affected by subgroups of potential risk confounders. Results A total of 172 patients with an average age of 72 years were analyzed, of which 59.9% (n = 103) were females. 66% were hypertensive and 40% had atrial fibrillation (AF). The best cutoff value of VFA for all-cause death was 148.3cm2. The all-cause mortality rate in the VFA ≥ 148.3 cm2 group was significantly higher than in the VFA 2 group. Patients with higher VFA were older, with higher body mass index (BMI), and more frequently with pre-existing hypertension and atrial fibrillation. Age, smoking, BMI, H2PEFF score, and VFA were significantly associated with higher mortality in HFpEF by univariable Cox analysis. However, PAT thickness, EAT thickness, waist/hip ratio, body fat mass, and abdominal obesity were not effective predictors of HFpEF outcomes. After adjusting for cofounders of other underlining risk factors, VFA could independently predict all-cause mortality in HFpEF. In addition, results were broadly consistent in participants with different baseline characteristics. Conclusions VFA may be a useful prognostic risk factor for all-cause mortality in patients with HFpEF. Trial registration NCT05496439 (08/10/2022), retrospectively registered.