INTRODUCTION: Cilostazol has been widely used to prevent peripheral vascular events after PCI. However, guidelines in cilostazol-based triple antiplatelet therapy for patients with ischemic heart disease undergoing PCI remain unclear. The purpose of this study was to assess the efficacy and safety of DAPT (aspirin and clopidogrel) compared to cilostazol -based TAPT (aspirin, clopidogrel and cilostazol). METHODS: We conducted a comprehensive search of the Medline, Embase, Scopus, Cochrane, and Web of Science databases until November 2024 to identify RCTs comparing DAPT with cilostazol -based TAPT in patients with ischemic heart disease undergoing PCI. Pooled risk ratios (RRs) with 95% CIs were calculated. RESULTS: Eight RCTs (5,299 patients) were included in this systematic review and meta-analysis. A significantly reduced risk of all-cause mortality in hospital was observed with DAPT compared to cilostazol -based TAPT (RR: 0.27, 95% CI: 0.07 to 0.94, p = 0.04). Also, A significantly reduced risk of headache and palpitation was observed with DAPT compared to cilostazol -based TAPT, with pooled RR (RR: 0.15, 95% CI: 0.06 to 0.33, p <
0.001) and (RR: 0.24, 95% CI: 0.08 to 0.73, p = 0.01), respectively. However, no difference was observed between DAPT and cilostazol -based TAPT on vessel revascularization, stroke, stent thrombosis, myocardial infarction and major adverse cardiac events. CONCLUSION: Aspirin and clopidogrel were associated with a lower risk of adverse events compared to cilostazol-based TAPT. However, the addition of cilostazol did not improve clinical outcomes. Further trials are needed to clarify the role of cilostazol -based TAPT for patients with ischemic heart disease undergoing PCI.