The patient population with the need for oral anticoagulation to reduce stroke risk associated with atrial fibrillation (AF) and dual antiplatelet therapy to prevent stent thrombosis and myocardial infarction after percutaneous coronary intervention is increasing. However, patients treated with a triple therapy consisting of oral anticoagulation, aspirin, and a P2Y12 inhibitor have been demonstrated to be at high bleeding risk. The best combination of these agents and the duration of the different therapies are still uncertain. Recently, data on the safety of combinations including nonvitamin K antagonists have been published and evidence for the feasibility of a dual therapy is increasing. This review aims to provide insights to the pathophysiology of thrombus formation in AF versus coronary artery disease, summarize available data on postprocedural treatment strategies, and report current guidelines for AF patients after percutaneous coronary intervention. Furthermore, the role of stent type selection and tools to evaluate as well as strategies to reduce the individual bleeding risk will be discussed.