This is a systematic review and meta-analysis of the safety and effectiveness of short-duration over the standard-duration of dual antiplatelet therapy (DAPT) in patients with high bleeding risk (HBR) undergoing percutaneous coronary intervention with the implantation of drug-eluting stents. Eight randomized controlled trials were found using a comprehensive search of databases PubMed, Embase, Cochrane Central, and Scopus databases and have a total of 12,467 patients and were published within 2015 to 2023. Short term DAPT (≤3 months) was compared to standard including DAPT (≥6 months). The major bleeding and major adverse cardiovascular events (MACE) constituted the primary outcomes, whereas stent thrombosis, myocardial infarction, and all-cause mortality were the secondary outcomes. The pooled analysis showed that the risk of major bleeding was significantly decreased with abbreviated DAPT (RR 0.68; 95% CI 0.54–0.85; p = 0.001) with low levels of heterogeneity (I² = 21%). No statistically significant difference existed in MACE (RR 1.04; 95% CI 0.90–1.20; p = 0.62), stent thrombosis, myocardial infarction or all-cause mortality between the two strategies. The assessment of the risk of bias showed that overall there was low methodological bias in the included trials. These results indicate that short-course DAPT offers better bleeding safety with little ischemic protection loss in selectively chosen HBR patients. New, large-scale research and longer-term follow-up is justified in conserving the long-term results and correct the customized treatment plans.