Objective：This study aims to detect the differential expression profile of platelet miRNAs（miRNA）in patients with coronary artery disease（CAD）and clopidogrel low response（CLR）. Methods：A total of 78 CAD patients with clopidogrel treatment（loading dose 300 mg and maintenance dose 75 mg/d）at least 5 days were consecutively enrolled. Adenosine diphosphate（ADP）induced platelet aggregation（PLADP）was tested by light transmittance aggregation（LTA）. Nineteen patients whose PLADP were at upper quartile were defined as CLR group，while another nineteen patients at lower quartile were selected as control. The total RNA of leukocyte depleted platelet（LDP）were extracted from each of the selected patients，and the extracted total RNA from the two groups were mixed into two RNA pools respectively. After two RNA pools were qualified by RNA denaturation electrophoresis，the differential expression profiles of platelet miRNAs were screened by high-throughput sequencing. The target gene predicting software including TargetScan，miRanda，PITA and miRWalk were adopted to explore the miRNAs that modulate the key protein in the process of platelet aggregation. Results：Baseline clinical characteristics of the two groups showed no significant difference. The PLADP level of the CLR group was significantly higher than that of the control group（P < 0.000 1）. The total RNA pools of the two groups were detected by RNA denaturation electrophoresis and no significant degradation was found. 95 platelet miRNAs were differently expressed by high-throughput sequencing between the two groups，among which 20 miRNAs（hsa-miR-300，hsa-miR-151b，hsa-miR-1299，et al）were 2-fold down-regulated in CLR patients，and 8 miRNAs（hsa-miR-188-5p、hsa-miR-6874-3p、hsa-miR-218-5p、hsa-miR-3150b-3p、hsa-miR-1288-3p、hsa-miR-1299、hsa-miR-6862-5p、hsa-miR-4421）were identified by at least two target gene predicting software as having regulatory effects on key proteins associated with platelet aggregation. Conclusion：There is a significant downregulation of platelet miRNAs in CLR patients. We successfully screen 8 miRNAs that could modulate the key protein in the process of platelet aggregation，which is warrant to be investigated in future study.