The objective of this study was to explore the long-term effect of cilostazol-optimized antiplatelet therapy after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). One hundred forty-six patients with ACS who underwent PCI were enrolled. Patients were randomly divided into 2 groups based on clot rate (CR), and both groups received antiplatelet therapy: aspirin and clopidogrel plus cilostazol (intensification group, n = 72) or aspirin and clopidogrel (control group, n = 74). Clinical follow-up was up to 12 months after PCI. During follow-up, CR was determined at day 1 and at 1, 3, 6, and 12 months post-PCI. Efficacy endpoints included second acute myocardial infarction, in-stent thrombosis, revascularization (second PCI), sudden death, and hemorrhage. CR was significantly lower in the intensification group than in the control group at 1, 3, and 6 months after PCI (P < 0.05). The incidences of second acute myocardial infarction, in-stent thrombosis, revascularization (second PCI), and sudden cardiac death were also lower but insignificant; there were no hemorrhage events (P > 0.05). Cilostazol-optimized antiplatelet therapy can significantly decrease CR after PCI in patients with acute coronary syndrome.