Objective:To evaluate the efficacy and safety of double-dose clopidogrel compared with routine-dose dual anti-platelet treatment (DAPT)in patients with clopidogrel low response (CLR)after percutaneous coronary intervention (PCI). Methods:Ninety-two CLR patients were screened by light transmission aggregometry (LTA)after PCL and randomly divided into the clopidogrel routine-dose group and the clopidogrel double-dose group after taking routine-dose aspirin and clopidogrel for more than five days. Platelet aggregation was determined by LTA one-month post-randomization. The patients were followed up and all clinical events were recorded for one year. Results:There was no significant difference of adenosine diphosphate induced platelet aggregation (PLADP)between the two groups at baseline (P > 0.05). However,the PLADP level of the double-dose group was significantly lower than that of the routine-dose group at one-month follow-up (P < 0.001). The major adverse event rates of the two groups were both 4.3%. The double-dose group presented less secondary adverse events compared with the double-dose group,mainly attributed to cardiac rehospitalization (P < 0.01). The two groups showed comparable major bleed events (0% vs. 0%),as well as minor and minimal bleeding events (0% vs. 0% and 10.9% vs. 10.9%,respectively). Conclusion:Double-dose clopidogrel can significantly improve the ADP-induced platelet aggregation during the first month and may lower the cardiac rehospitalization event without excessive risk of bleeding in CLR patients undergoing PCI during one-year follow-up.