The use of aspirin and a P2Y receptor antagonist as dual antiplatelet therapy (DAPT) has become the treatment of choice in patients with acute coronary syndrome (ACS) and percutaneous coronary intervention to prevent recurrent thrombotic events. Although DAPT is beneficial for most patients, few patients still experience recurrent thrombotic events and increased bleeding episodes. This article reviews current literature to identify various approaches that may enhance the DAPT benefit-risk ratio in patients with ACS. Three strategies addressed in this article include the following-(1) use of more potent antiplatelet agents other than clopidogrel; (2) addition of direct oral anticoagulants (DOACs) to DAPT; and (3) optimizing DAPT duration. Although the use of prasugrel or ticagrelor improves treatment efficacy, their use has been associated with increased risk of bleeding compared to clopidogrel. The combination of DOACs and DAPT may not be the most viable strategy because of its limited cardiovascular benefits and increased bleeding risks. The optimal duration of DAPT duration remains controversial. Most guidelines recommend 6 to 12 months of DAPT, whereas emerging studies have shown benefit for both shorter and longer duration of treatment. Risk stratification tools such as the DAPT score may play a role in individualizing DAPT duration according to patient's ischemic and bleeding risks.