As per current guidelines, acute coronary syndrome (ACS) patients who undergo percutaneous coronary intervention (PCI) should be started on dual antiplatelet therapy (DAPT) for a period of 12months. To assess the efficacy and safety of brief DAPT (up to 3months) succeeded by ticagrelor monotherapy compared with a 12-month DAPT in ACS patients following PCI. We systematically searched Cochrane, Embase, and PubMed to find relevant randomized clinical trials. Examined outcomes included the incidence of major adverse cerebrovascular and cardiovascular events (MACCE), bleeding events, and the composite incidence of net adverse clinical events (NACE). Our primary analysis included 21,927 ACS patients from six RCTs. Our pooled results indicate that following PCI in individuals with ACS, brief DAPT followed by ticagrelor did not increase the risk of MACCE (OR 0.92, 95% CI 0.79-1.07) but significantly reduced the risk of minor or major bleeding (OR 0.52, 95% CI 0.44-0.62) and NACE (OR 0.71, 95% CI 0.59-0.86) compared with a long-term DAPT within a follow-up of 12months. Brief DAPT followed by ticagrelor monotherapy is superior to a 12-month DAPT in offering a net clinical advantage in ACS patients following PCI.