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Aim: This meta‐analysis was carried out to explore if a personalized antiplatelet strategy based on genotyping is superior to conventional therapy. Methods: PubMed, Web of Science, EMBASE and the Cochrane Library were searched from the inception of each database to 5 May 2020. Studies reporting endpoints in genotype‐guided treatment group and conventional treatment group were included. The endpoint results were presented as the risk ratio (RR), with 95% confidence interval (CI). Results: A total of 10 561 patients from 16 studies (eight randomized controlled trials [RCT] and eight cohort studies) were included in the meta‐analysis. The rates of major adverse cardiovascular events (MACE), stent thrombosis and myocardial infarction (MI) were significantly lower in the genotype‐guided group than in the conventional treatment group (RR 0.56, 95% CI 0.44‐0.73, P <.0001; RR 0.40, 95% CI 0.24‐0.67, P =.0005; RR 0.45, 95% CI 0.35‐0.58, P <.00001, respectively). A significant difference was found between the two groups in major bleeding (RR 0.73, 95% CI 0.55‐0.98, P =.04), which was not robust after sensitivity analysis. Conclusion: Genotype‐guided antiplatelet treatment could decrease the risk of MACE, stent thrombosis and MI in patients with coronary artery disease or undergoing percutaneous coronary intervention, without increasing the risk of bleeding over a long follow‐up period. The decreased risk of efficacy outcomes was more obvious in cohort studies. Well‐organized RCTs and clinical trials are required to verify the benefit of genotype‐guided therapy. [ABSTRACT FROM AUTHOR]