Background: Optimal inhibition of platelet aggregation by dual antiplatelet therapy(DAPT) is critical in patients with acute myocardial infarction(AMI). Recently, concerns have been raised for the reduced efficacy of clopidogrel when administered concurrently with proton pump inhibitor (PPI), frequently used for increased risk of gastrointestinal bleeding in patients with DAPT. However whether adjunctive cilostazol to DAPT (triple antiplatelet therapy) can inhibit enhanced platelet reactivity in patients with AMI using PPI has not been elucidated yet. The aim of this study was to assess the efficacy of triple antiplatelet therapy for platelet inhibition in patients with AMI using PPI. Method: Immediately after emergency room arrival, patients with AMI received clopidogrel (600-mg loading dose, followed by 75 mg daily) and aspirin (300-mg loading dose and 200 mg daily throughout the study period). After patients underwent coronary stenting (n=90), patients were randomly assigned to receive either adjunctive cilostazol (triple group; n = 30) with omeprazole 20mg or high maintenance dose (MD) clopidogrel (high-MD group; n = 30) with omeprazole 20mg. Platelet reactivity was assessed at predischarge and 30-day follow-up by conventional aggregometry. Vasodilator-stimulated phosphoprotein (VASP) assay was assessed at 30-day follow-up. Results: Predischarge platelet reactivities were similar in both groups. At 30-day follow-up, maximal aggregation and late aggregation with 20 關M/l ADP stimuli was significantly lower in the triple group with omeprazole versus high-MD group with omeprazole (34.6 짹 15.6% vs. 45.7 짹 20.1%, P = 0.02 and 22.8 짹 15.9 % vs. 35.3 짹 23.1%, respectively, P = 0.019). But there was no differences of maximal and late aggregation between triple group with omeprazole and high MD group with omeprazole when 5 關M/l ADP was used. Platelet reactivity ratio by VASP assay at 30-days of follow-up were significantly lower in triple group with omeprazole compared to high MD group with omeprazole (36.0 짹 13.7% vs. 44.4 짹 16.8%, P = 0.039). With respect to high-postclopidogrel platelet reactivity (prespecified as 20 關M ADP-induced maximal aggregation > 50% of light transmission), fewer patients in the triple group with omeprazole (16.7%) met the criteria as compared with those in high-MD groups with omeprazole (33.3%) at 30-day follow-up but it has no significance (P = 0.233). Conclusions: Among patients with AMI using proton pump inhibitor, triple antiplatelet therapy achieves a greater antiplatelet effect at 30 days as compared with a high-MD clopidogrel.