Dual anti-platelet therapy (DAPT), comprising aspirin and a P2Y ₁₂ receptor antagonist, is recommended following stent implantation during percutaneous coronary intervention (PCI). Up to 10% of patients undergoing PCI have a prior indication for long-term oral anticoagulation (OAC), such as atrial fibrillation (AF) or a mechanical heart valve in situ . For patients undergoing PCI with a prior indication for long-term oral anticoagulation (OAC; with a vitamin K antagonist, or novel oral anticoagulant), preventing thromboembolic events, without increasing the risk of major hemorrhage, remains challenging. Recent guidelines emphasise formal assessment of hemorrhagic risk (i.e. using the HAS-BLED score) and stroke risk (CHA ₂ DS ₂ -VAS _C ) and vary depending on the setting of PCI (CCS or ACS). For example, in patients with a low baseline bleeding risk (HAS-BLED 0-2), and significant risk of stroke (CHA ₂ DS ₂ -VAS _C ≥2), undergoing elective PCI, four weeks of OAC (preferably NOAC) +DAPT, followed by OAC (preferably NOAC) and clopidogrel alone until six months post-procedure, and lifelong OAC (preferably NOAC) thereafter. If thrombotic risk is low or there are concerns about a prevailing bleeding risk then early cessation of aspirin (≤1 week) is recommended. This chapter reviews the efficacy and safety of combinations of traditional antiplatelet drugs and OAC agents, summarizes up-to-date, evidence-based clinical guidelines, and addresses the questions that remain unanswered with regard to the optimisation of antithrombotic pharmacotherapy.