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Background: This study explores the association between HSP22/27/60 and the occurrence of STEMI and the prognosis after PCI to compensate for the insufficient risk stratification in the current situation. Methods: This study included 88 patients with STEMI and 90 patients with stable coronary artery disease who were admitted to our hospital. ELISA detected serum levels of HSP22/27/60 to analyze their correlation with STEMI. Dynamic monitoring was conducted on the STEMI group (from before to 4 days after the operation) to evaluate the relationship between the changes in HSP levels and the occurrence of MACE. Results:The serum levels of HSP22/27/60 in STEMI patients were significantly higher than in the control group (P < 0.05). ROC curve analysis showed that these three markers had high diagnostic values for STEMI. The levels of HSP22/HSP27 in STEMI patients peaked on the third day after PCI, while HSP60 peaked at 8 hours after the operation. After 6 months of follow-up, 15 of 88 STEMI patients developed MACE. The predictive value of peak HSP levels for MACE was the highest when HSP22/27/60 were jointly predicted, with an AUC of 0.917 (95% CI: 0.857 - 0.977). Multivariate binary Logistic regression analysis showed that after adjusting for creatinine and N-terminal pro-brain natriuretic peptide, HSP22/27/60 were all independent risk factors for MACE. Conclusions: The serum HSP22/27/60 levels in STEMI patients were significantly increased and had diagnostic value. Its postoperative peak value (especially combined detection) can predict the risk of MACE after PCI and is a potential prognostic marker.