Aim To explore the relationship between soluble growth stimulation expressed gene 2 (sST2) and myocardial fibrosis after acute myocardial infarction (AMI). Methods 249 cases were selected from January 2015 to September 2016 in the First Hospital of Lanzhou University, AMI group had 166 cases that were first diagnosed as AMI patients, while 83 cases of coronary angiography negative in the control group. The level of serum sST2, procollagen Ⅲ N-terminal peptide (PIIINP), aminoterminal pro-brain natriuretic peptide (NT-proBNP) were tested and left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) were collected, compared and analyzed. Results Serum sST2, PⅢNP and NT-proBNP levels and values of LVESV and LVEDV in AMI group were higher than those in control group, values of LVEF in AMI group were lower than those in control group (P＜0.05 or P＜0.01). Serum sST2 level in LVEF＜50% subgroup of AMI group was higher than LVEF≥50% subgroup (P＝0.031). Serum levels of sST2 were positively correlated with PⅢNP (r＝0.181, P＝0.02), and negatively correlated with LVEF (r＝－0.179, P＝0.021) in group AMI. Serum sST2, NT-proBNP and sST2＋NT-proBNP in AMI group could diagnose heart failure after AMI, and their areas under ROC curve were 0.8,0.683 and 0.732 respectively. Conclusion Serum sST2 participates in the process of myocardial fibrosis after AMI, and is correlated with left ventricular systolic function. Serum sST2 levels have diagnostic value in heart faliure after AMI.