Updated project metadata. Background: Heart failure with preserved ejection fraction (HFpEF) has become a major public health problem with a morbidity and mortality similar to heart failure with reduced ejection fraction (HFrEF). Recently, it has been proved epicardial adipose tissue (EAT) played an important role in the pathogenesis of HFpEF, however the underlying mechanisms are not yet fully elucidated. This study attempted to describe comprehensive proteomic analysis of EAT in HFpEF patients and non-HF patients as controls, and identify local candidate molecules characterizing EAT in HFpEF patients. EAT samples were collected from patients undergoing heart surgery in two groups. Proteins was identified in liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted and protein-protein interaction network was constructed with Cytoscape software. A total of 2416 proteins were identified in LC-MS/MS experiments and 2349 proteins were quantified. Amongst them, totally 96 significant proteins (including 71 upregulated proteins in abundance and 25 downregulated proteins) were differently expressed between HFpEF and non-HF group. GO-enrichment, KEGG pathway analysis and interaction network construction showed these differentially expressed proteins were predominantly involved in HFpEF-related processes including lipid metabolic disorder, inflammation and mitochondrial dysfunction including FABP5, CD36, CFB, ADSL, POSTN, TRAP1 et al., which might contribute to the pathogenesis of HFpEF. In conclusion, this is the first demonstration to describe the parts of EAT proteome in HFpEF patients. Our findings provide a comprehensive understanding for linking EAT to the pathogenesis of HFpEF, which may offer new insights into the treatment of HFpEF targeting on EAT.