Abstract: This study was designed to determine whether CES1A −816A/C polymorphism could be associated with altered clopidogrel response. Recruited patients were pretreated with 300 mg clopidogrel loading dose before undergoing percutaneous coronary intervention for stenting and genotyped with CYP2C19 *2, *3, or *17, and CES1A −816A/C, respectively. Adenosine diphosphate–induced maximum platelet aggregation (MPA) was determined on day 3 after initiation of daily clopidogrel maintenance doses. The clinical primary end point was the 1-year incidence of definite stent thrombosis (ST). Multivariable linear regression revealed that the CES1A −816A/C polymorphism was independently associated with MPA measures with an absolute β value of 6.76. Of 617 patients, a subcohort of 249 patients not carrying CYP2C19 *2, *3, or *17 were categorized into 3 groups based on the −816A/C genotype. The median MPA value was lower in 125 carriers of the −816C variant than in 124 noncarriers (21.5% vs. 31.7%, P = 0.001). The 1-year definite ST occurred in 7 patients in that subcohort, and only 1 ST case was one of carriers of the −816 A/A that was associated with higher MPA values. The CES1A −816C would be used to predict greater platelet response to clopidogrel than the CES1A −816A in percutaneous coronary intervention–treated patients not carrying CYP2C19 variants.