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Serum metabolite profiling of ST-elevation myocardial infarction (STEMI), unstable angina (UA) and healthy controls was performed using gas chromatography mass spectrometry (GC\/MS), solid-phase microextraction coupled to gas chromatography mass spectrometry (SPME-GC\/MS) and nuclear magnetic resonance (<jats:sup>1<\/jats:sup>H-NMR). Multivariate data analysis revealed a metabolic signature that could robustly discriminate STEMI patients from both healthy controls and UA patients. This panel of biomarkers consisted of 19 metabolites identified in the serum of STEMI patients. One of the most intriguing biomarkers among these metabolites is hydrogen sulfide (H<jats:sub>2<\/jats:sub>S), an endogenous gasotransmitter with profound effect on the heart. Serum H<jats:sub>2<\/jats:sub>S absolute levels were further investigated using a quantitative double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). This highly sensitive immunoassay confirmed the elevation of serum H<jats:sub>2<\/jats:sub>S in STEMI patients. H<jats:sub>2<\/jats:sub>S level discriminated between UA and STEMI groups, providing an initial insight into serum-free H<jats:sub>2<\/jats:sub>S bioavailability during ACS. In conclusion, the current study provides a detailed map illustrating the most predominant altered metabolic pathways and the biochemical linkages among the biomarker metabolites identified in STEMI patients. 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