The recommended treatment following an acute coronary syndrome (ACS) typically involves 12 months of dual antiplatelet therapy (DAPT). During the initial stages after the ACS event, there is a high ischemic risk, which gradually decreases over time. Conversely, the risk of bleeding remains relatively constant. This trend has led to the development of a treatment paradigm focused on ensuring robust platelet inhibition and ischemic protection, particularly in the first month post-ACS, followed by a greater emphasis on minimizing bleeding risk in the chronic phase. This approach involves transitioning from more potent oral P2Y12 inhibitors, such as prasugrel or ticagrelor, to a less potent agent like clopidogrel, or reducing the dosage of the P2Y12 inhibitor, for example, lowering prasugrel to 5 mg, after an initial period of DAPT with potent P2Y12 inhibitors. Widely known as “de-escalation,” this therapeutic approach is gaining recognition as one of the most promising strategies for tailoring antiplatelet therapy to ACS patients. The reduction in potency can be “unguided” and left to the discretion of the physician or “guided” by platelet function test (PFT) or genetic tests. The relative effectiveness and safety of unguided versus guided reduction remain uncertain, and the practical implementation of guided reduction is constrained by the availability of necessary assays in routine clinical practice. Moreover, important questions persist about the optimal timing, suitable candidates for de-escalation, and the comparative effectiveness of alternative strategies aimed at maximizing the overall benefits of antiplatelet therapy for ACS.