OBJECTIVES: To evaluate the cost-effectiveness, from the Hong Kong healthcare perspective, of CYP2C19 genotype-guided selection of antiplatelet therapy compared with universal use of clopidogrel or ticagrelor (irrespective of genotype) for acute coronary syndrome (ACS) patients who underwent percutaneous coronary intervention (PCI).  METHODS:  A two-part model consisting of a 1-year decision tree and a lifetime Markov model was developed to compare: (i) generic clopidogrel or ticagrelor based on CYP2C19*2 genotype (52% carriers locally), (ii) universal clopidogrel and (iii) universal ticagrelor. Risks of non-fatal myocardial infarction, non-fatal stroke, stent thrombosis, major bleeding and death were estimated from the Asian sub-study of PLATO. The Markov model was built to simulate the progress of a typical cohort of 60-year-old Chinese patients with ACS undergoing PCI. Follow-up was until age 85 years. Costs were estimated from a prospective PCI registry in a Hong Kong tertiary referral hospital, and expressed in 2016 Hong Kong dollars (HKD). All costs and quality-adjusted life-years (QALYs) were discounted at an annual rate of 3%. Incremental cost-effectiveness ratios (ICERs) of < HKD 268,333 (1 time GDP of Hong Kong) were considered cost-effective.  RESULTS: Universal ticagrelor use was cost-effective compared with universal clopidogrel (ICER= HKD 64,039/QALY). With CYP2C19 genetic testing at a minimum cost of HKD117 (USD15), genotype-guided antiplatelet therapy was dominant compared to universal ticagrelor. Sensitivity analysis showed that under the ceiling price of HKD17,711 (USD2270), genotype-guided therapy remained a cost-effective strategy compared with universal clopidogrel or ticagrelor. CONCLUSIONS:  CYP2C19*2 genotype-guided antiplatelet therapy selection was considered a cost-effective strategy compared to either unselected generic clopidogrel or ticagrelor in ACS patients after PCI in Hong Kong.