Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor blocker is the standard antithrombotic treatment after percutaneous coronary intervention (PCI), irrespectively of the clinical presentation, either acute coronary syndrome (ACS) or chronic coronary syndrome (CCS). In specific clinical scenarios, appropriate adjustment of DAPT duration and drug could be made, balancing bleeding with ischemic risk. In ACS, the default DAPT strategy includes aspirin and prasugrel (preferentially) or ticagrelor for 12 months. In high bleeding risk patients’ bleeding, mitigation strategies should be considered. These consist in DAPT duration shortening and/or P2Y12 de-escalation. In CCS, the default DAPT strategy includes aspirin and P2Y12 inhibitor (clopidogrel) for 6 months. In this case de-escalation strategy consists of DAPT shortening, ranging from 1 to 3 months.