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Background In TAILOR-PCI, genotype-guided selection of P2Y 12 inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD-GENE score for tailoring P2Y 12 inhibitor selection after percutaneous coronary intervention. Methods and Results In a post hoc analysis of the TAILOR-PCI, outcomes were analyzed by ABCD-GENE score and allocation to genotype-guided or conventional P2Y 12 inhibitor selection. Primary (death, myocardial infarction, or stroke) and secondary (cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia) outcomes were assessed. Among 3883 patients discharged on clopidogrel in the genotype-guided and conventional therapy groups, 15.8% and 84.2% had high (≥10 points) or low (<10) ABCD-GENE scores, respectively. At 12 months, both the primary (5.2% versus 2.6%, P <0.001) and secondary outcomes (7.7% versus 4.6%, P =0.001) were significantly increased in patients with high ABCD-GENE score. Among 4714 patients allocated to genotype-guided or conventional therapy, the former did not significantly reduce the 12-month risk of the primary and secondary outcomes in both the high and low ABCD-GENE score groups (p interaction =0.48 and 0.27, respectively). Conclusions Among patients with percutaneous coronary intervention on clopidogrel, the ABCD-GENE score was helpful in identifying those at higher risk. The ABCD-GENE score may potentially enhance the precision of tailored selection of P2Y 12 inhibitors, which needs to be confirmed in prospective investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01742117.