Myocardial infarction (MI) and unstable angina (UA) exhibit overlapping symptoms, yet they require distinct management approaches. Identifying the metabolic differences between MI and UA may facilitate more precise diagnosis and treatment.Metabolomic analysis was conducted on 95 patients, comprising 33 UA patients, 38 MI patients, and 24 normal controls. Serum metabolites were profiled using tandem mass spectrometry coupled with liquid chromatography.Metabolic analysis revealed notable differences in several metabolites, including xylidine, hydroxycaproic acid, butylbenzenesulfonamide, octanetriol, phosphocholine, and medronic acid, between MI and UA. These metabolites displayed promising diagnostic capabilities for distinguishing between MI and UA. Pathway analysis identified connections with cardiac hypertrophy, Wnt signaling, and fatty acid oxidation.Potential metabolite biomarkers and pathways differentially altered in MI compared to UA were identified in this metabolomics study. The results provide new insights into the metabolic signatures of these ischemic heart diseases. With further confirmation, improved early diagnosis and personalized treatment approaches could be facilitated.Copyright © 2024 Elsevier B.V. All rights reserved.