Background Using epicardial adipose tissue thickness (EATt) and neutrophil-to-lymphocyte ratio (NLR) as individual indicators provides beneficial insight into the prognosis of patients suffering from heart failure with preserved ejection fraction (HFpEF). Aim In our study, we aimed to evaluate whether the combined evaluation of NLR and EATt would provide an advantage for identifying high-risk HFpEF patients according to hospitalization for heart failure (HHF) and left ventricular diastolic dysfunction (LVDD). Method A total of 168 outpatients with HFpEF were retrospectively analyzed. The predictive performance of two inflammatory variables was assessed by the receiver operating characteristic curve and a one-way analysis of variance (ANOVA) test. The patients were stratified into three distinct risk categories based on the established cut-off values for EATt and NLR as follows: Group I, high risk; Group II, middle risk; and Group III, low risk. Results Patients in Group I had the highest risk for HHF and the presence of LVDD (p=0.001 for HHF, p=0.011 for LVDD). Patients in Group I also exhibited more symptomatic and a greater number of comorbidities. In Group I, more structural remodeling (enlargedleft ventricular end-systolic volume index (LVESVI) and left atrial volume index (LAVI)) and associated signs of increased intracardiac pressure (elevated E/A ratio, medial E/e') were observed. Conclusion The results of our study indicate that the use of both EATt and NLR among patients with HFpEF may provide better accuracy in predicting HHF and LVDD compared to the use of either EATt or NLR alone.