Aim: To investigate the association between plasma S100A1 level and ST-segment elevation myocardial infarction (STEMI) and potential significance of S100A1 in post-infarction cardiac function. Methods: We examined the plasma S100A1 level in 207 STEMI patients (STEMI group) and 217 clinically healthy subjects for routine physical examination without a history of coronary artery disease (Control group). Baseline characteristics and concentrations of relevant biomarkers were compared. The relationship between S100A1 and other plasma biomarkers was detected using correlation analysis. The predictive role of S100A1 on occurrence of STEMI was then assessed using multivariate ordinal regression model analysis after adjusting for other covariates. Results: The plasma S100A1 level was found to be significantly higher (P<0.001) in STEMI group (3197.7±1576.0 pg/mL) than in Control (1423.5±1315.5 pg/mL) group. Furthermore, the correlation analysis demonstrated plasma S100A1 level was significantly associated correlated with hypersensitive cardiac troponin T (hs-cTnT) (r = 0.32; P < 0.001), creatine kinase MB (CK-MB) (r = 0.42, P < 0.001), left ventricular eject fraction (LVEF) (r =-0.12, P = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (r = 0.61; P < 0.001) and hypersensitive C reactive protein (hs-CRP) (r = 0.38; P < 0.001). Moreover, the enrolled subjects who with a S100A1 concentration ≤ 1965.9 pg/mL presented significantly better cardiac function than the rest population. Multivariate Logistic regression analysis revealed that S100A1 was an independent predictor for STEMI patients (OR: 0.671, 95% CI 0.500-0.891, P<0.001). In addition, higher S100A1 concentration (> 1965.9 pg/mL) significantly increased the risk of STEMI as compared with the lower level (OR: 6.925; 95% CI: 4.15-11.375; P<0.001). Conclusion: These results indicated that the elevated plasma S100A1 level is an important predictor of STEMI in combination with several biomarkers and also potentially reflects the cardiac function following the acute coronary ischemia.