Objective · To investigate the potential value of serum miRNAs for early diagnosis of acute coronary syndrome (ACS).  Methods · Blood samples were collected from 28 emergency patients with suspected ACS in 3 h after enrollment. Eighteen patients were finally diagnosed as ACS and ten as nonACS according to the ACS guideline. The expression levels of cardiac miR-499 and myocardial injury related miR-652 were measured with qRT-PCR. At the same time levels of troponin I (cTnI) were monitored. Then the correlations between miRNAs and cTnI were analyzed. In addition, 95% reference range was established.  Results · The expression levels of serum miRNAs increased in ACS patients within 3 h and serum miR-499 in the ACS patients was 9.2 times the amount in the non-ACS patients (P=0.009). Serum miR-499 (r=0.595, P=0.001) and miR-652 (r=0.579, P=0.001) levels both had positive correlations with cTnI. The area under the ROC curve (AUC) of serum miR-499 and miR-652 was 0.786 and 0.583, respectively. The sensitivity and specificity of miR-499 were 72.22% and 80.00%, respectively, while 72.22% and 60.00% for miR-652. The reference ranges of serum miR-499 and miR-652 were 0.001-2.723 and 0.122-9.660, respectively.  Conclusion · Cardiac miR-499 in serum has potential to be a biomarker for early diagnosis of ACS.