Coronary artery disease (CAD) remains the leading cause of mortality and morbidity around the world. Despite significant progress in the diagnosis and treatment of cardiovascular diseases, still there is a clinical need to identify novel biomarkers for early diagnosis and treatment of CAD. The aim of the study is to investigate circulating miRNAs in CAD patients to identify potential biomarkers for early detection and therapeutic management of CAD. We assessed the expression of different candidate miRNAs (miR-21-5p, miR-133a-3p, miR-221-3p, miR-451a and miR-584-5p) in plasma from 50 CAD patients and 50 controls by qRT-PCR analysis. The expression levels of miR-133a-3p (fold change (FC): 28.05, p < 0.0001), miR-451a (FC: 27.47, p < 0.0001), miR-584-5p (FC: 7.89, p < 0.0001), miR-21-5p (FC: 5.35, p < 0.0001) and miR-221-3p (FC: 5.03, p < 0.0001) were significantly up-regulated in CAD patients compared to controls. Receiver operating characteristic curve analysis showed that miR-133a-3p and miR-451a were powerful biomarkers for detecting CAD. Our results suggested that miR-21-5p, miR-133a-3p, miR-221-3p, miR-451a and miR-584-5p may serve as independent biomarkers for CAD. Further, the combination of miR-133a-3p and miR-451a could be used as a specific signature in CAD diagnosis.