Ischemic and bleeding events portend equivalently poor prognosis after percutaneous coronary intervention (PCI). Risk factors for these untoward events largely overlap limiting the “decoupling” of bleeding and ischemic risk. While individual patient risk scores inform the duration of guideline recommended dual antiplatelet therapy (DAPT) to strike the optimal balance between ischemic and bleeding risk, a promising additional approach is to tailor the regimens themselves. In higher risk patients, 1 month of aspirin plus ticagrelor followed by 23 months of ticagrelor monotherapy has equivalent bleeding and numerically improved ischemic risk than standard DAPT for 12 months followed by aspirin monotherapy in the GLOBAL LEADERS trial. In the TWILIGHT study of high ischemic and bleeding risk patients, 12 months of ticagrelor monotherapy had lower bleeding risk with equivalent ischemic risk as DAPT after 3 months of successful DAPT. Individual risk scores should be developed informing both optimal antiplatelet regimen such as ticagrelor monotherapy and treatment duration after PCI.