Background Omeprazole, usually used in the antiplatelet therapy during percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS), has been reported to increase ischemic events in retrospective studies. However, other clinical trials gave paradoxical results. The aim of this study was to assess the effects of omeprazole on clopidogrel efficacy and clinical events.Methods All patients (n=172) received aspirin (loading dose 300 mg and maintenance dose 100 mg/d) and clopidogrel (loading dose 600 mg and maintenance dose 75 mg/d) during the therapy. They were randomized to receive omeprazole (20 mg/d) or placebo for 30 days. Residual platelet activities in the adenosine 5'-diphosphate (ADP) pathway were detected on the fifth day after PCI with thrombelastography (TEG)-mapping. The clinical events were recorded after one month.Results According to the five levels of platelet activities, the frequency distributions of the inhibition rates were significantly different (P=0.0062). However, no significant change was seen in the distribution among the highest or the lowest inhibiting levels (＞95% and ＜30% inhibition rate). And there were no significant differences (P ＞0.05) in events incidence, while gastra-intesternal bleeding decreased in co-administration of omeprazole.Conclusions Omeprazole significantly blunts clopidogreal efficacy while not exacerbates ischimic events in ACS undergoing PCI. Omeprazaole even can decrease gastra-intestinal bleeding in those patients.