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Introduction: Long-term dual antiplatelet therapy (DAPT) has substantially reduced the risk of post-percutaneous coronary intervention (PCI) myocardial infarction and stent thrombosis at the expense of major bleeding. We hypothesized that a short-term DAPT followed by extended P2Y 12 inhibitor monotherapy might be appropriate for patients with both high ischemic and bleeding risks., Materials and Methods: We searched the databases: Pubmed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov to identify randomized trials assessing the antiplatelet strategies after PCI. The primary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The efficacy outcome was a composite of all-cause mortality/cardiovascular disease (CVD) death, myocardial infarction, or stroke. A random-effect model was used to calculate the pooled hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: We identified 5 randomized trials comparing P2Y 12 inhibitor monotherapy with standard DAPT (12 months) (16,057 versus 16,088). P2Y 12 inhibitor monotherapy following short-term DAPT (1 to 3 months) significantly reduced the risk of BARC type 3 or 5 bleeding compared to standard DAPT (pooled HR: 0.63, 95%CI: 0.46-0.86). The difference between P2Y 12 inhibitor monotherapy and standard DAPT in reducing the composite CVD outcomes was not statistically significant (HR: 0.88, 95%CI: 0.77-1.01)., Conclusions: P2Y 12 inhibitor monotherapy might be an effective strategy for lowering severe bleeding complications and simultaneously preserving the ischemic benefit in patients receiving PCI., (Copyright © 2020 Elsevier Ltd. All rights reserved.)