Background-Obstructive sleep apnea (OSA) is a novel risk factor for acute coronary syndrome (ACS). Several studies have shown OSA to be associated with induced platelet reactivity. However, whether OSA have effects on platelet function profiles in ACS patients taking dual antiplatelet therapy remains unexplored. Methods and Results-This was a cross-sectional observational study, in which ACS patients taking maintenance aspirin and clopidogrel therapy were included. OSA was defined as an apnea-hypopnea index = 15 events/hour. The inhibitory rate of arachidonic acid or adenosine diphosphate pathway were assessed with thrombelastography and defined patients with high residual on-treatment platelet reactivity. Platelet indices were obtained from routine analysis of blood samples using an automated blood cell counter. A total of 127 ACS patients taking dual antiplatelet therapy were analyzed. Platelet volume indices, including mean platelet volume and platelet large cell ratio, were significantly increased in patients with OSA. Patients with OSA (n=68) had significantly lower inhibitory rate of adenosine diphosphate receptor pathway (P=0.028) compared with those without (n=59). After adjustment for potential confounders, patients with OSA were more likely to have high residual on-treatment platelet reactivity after clopidogrel therapy (adjusted odds ratio: 3.25, 95% confidence interval: 1.19-8.87, P=0.021). Conclusions-In ACS patients taking dual antiplatelet therapy, OSA is associated with an increased level of platelet volume indices, reduced clopidogrel-induced antiplatelet effects and a greater prevalence of high residual on-treatment platelet reactivity.