Background: Dual antiplatelet therapy reduces major cardiovascular events in patients with ischemic heart disease and is also associated with increased risk of bleeding. Proton pump inhibitors (PPI) are recommended among high risk patients for gastrointestinal bleeding. Meanwhile, the activation of clopidogrel could be attenuated by PPI���s competitive inhibition of cytochrome P450 2C19 (CYP2C19). Cilostazol is free from the metabolism of CYP2C19 and has no pharmacokinetic interaction with PPI. Moreover, it showed similar platelet inhibition, as compared with clopidogrel in CYP2C19 mutant carriers. The aim of this study was to assess the antiplatelet effects of Cilostazol in patients receiving PPI. Methods: We consecutively enrolled 120 PPI-free patients who had been on clopidogrel (75 mg daily) and aspirin (100 mg daily) for at least 6 months after PCI. The patients were randomly assigned to either cilostazol 200 mg with lansoprazole 30 mg or clopidogrel 75 mg with lansoprazole 30 mg on top of aspirin treatment. Platelet reactivity (PR) was measured just after the randomization and at 14-day follow-up by light transmittance aggregometry (LTA) and VASP-PRI assay. Primary end point was inhibition of PRI. High on-treatment PR (HPR) was defined as VASP-PRI >50%. Results: Baseline platelet reactivity did not differ between the groups. At 14 day follow-up, Platelet reactivity by VASP-PRI was significantly increased during concomitant use of PPI (59.2짹17.2% vs. 66.2짹13.8%, p<0.001). However, cilostazol group had similar platelet inhibition with clopidogrel group (60.6짹17.0% vs. 57.6짹17.2%, p=0.35). The rate of HPR was also significantly increased after use of PPI (70.7% vs. 89.5%, p=0.034). However, it was not different between the groups (92.7% vs. 86.4%, p=0.37). Notably, Maximal platelet aggregation (MPA) by 0.5 mM-arachidonic acid stimuli was significantly decreased in cilostazol group (25.8짹18.2% vs. 10.2짹6.1%, p<0.001). MPA by 6 關g/ml-collagen stimuli was also significantly decreased (55.2짹19.0% vs. 45.1짹18.0%, P<0.001). However, these changes are not observed in the clopidogrel group. Conclusion: Lansoprazole inhibits the antiplatelet effects of clopidogrel in long-term maintenance phase of treatment. Cilostazol achieves similar antiplatelet effects with clopidogrel during concomitant use of lasoprazole. Moreover, it attenuated the platelet activation by other agonists. Therefore, cilostazol might be the excellent alternative to clopidogrel in patients receiving PPI.