AIMS: This study aims to assess the cost-effectiveness in Australia of screening CYP2C19 loss-of-function (LoF) alleles to guide selection of clopidogrel or ticagrelor for individuals with acute coronary syndrome who are likely to undergo coronary stenting. METHODS: Three treatment strategies were compared: universal clopidogrel therapy, universal ticagrelor therapy and genotyping CYP2C19 with use of ticagrelor for individuals with a LoF allele and clopidogrel for individuals without a LoF allele. Lifetime costs and quality-adjusted life years for each treatment strategy were estimated using a Markov model. The risks of events were primarily derived from the genetic substudy of the pivotal randomized controlled trial. RESULTS: CYP2C19 genotyping resulted in greater effectiveness and was cost-effective when compared with universal use of clopidogrel. However, universal use of ticagrelor was the most effective strategy overall and the incremental cost-effectiveness compared with the genotyping strategy was generally within what is considered acceptable. CONCLUSION: Ticagrelor is likely to be cost-effective even for individuals not carrying a CYP2C19 LoF allele.