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Background High on-treatment platelet reactivity has been associated with poor outcomes following acute coronary syndromes ( ACS). Both the loss of function CYP 2 C 19*2 allele and the gain of function CYP 2 C 19*17 allele along with a range of clinical characteristics have been associated with variation in the response to clopidogrel. Aim The study aims to examine the frequency of CYP2 C19 variants and understand the factors associated with on-treatment platelet reactivity in a New Zealand ACS population. Methods We prospectively enrolled 312 ACS patients. We collected clinical characteristics and measured on-treatment platelet reactivity using two validated point-of-care assays, VerifyNow and Multiplate. DNA was extracted and CYP 2 C 19*2 and *17 alleles were identified using real-time polymerase chain reaction. Results CYP 2 C 19*2 or CYP 2 C 19*17 alleles were observed in 101 (32%) and 106 (34%) of patients, respectively, with significant differences in distribution by ethnicity. In Maori and Pacific Island patients, 47% (confidence interval ( CI) 31-63%) had CYP 2 C 19*2 and 11% ( CI 4-19%) CYP 2 C 19*17 compared with 26% ( CI 19-32%) and 41% ( CI 32-49%) in white people. Carriage of CYP 2 C 19*2 alleles was associated with higher levels of platelet reactivity measured by either assay, but we observed no relationship between platelet reactivity and CYP 2 C 19*17. In multivariate analysis diabetes, clopidogrel dose and CYP 2 C 19*2 status were all significant independent predictors of platelet reactivity. Conclusions Both CYP 2 C 19*2 and *17 were common in a New Zealand ACS population, with CYP 2 C 19*2 observed in almost half the Maori and Pacific Island patients. CYP 2 C 19*2, diabetes and clopidogrel dose were independent contributors to on-treatment platelet reactivity. [ABSTRACT FROM AUTHOR]