The ideal antithrombotic management in patients with atrial fibrillation undergoing elective percutaneous coronary intervention or in acute coronary syndrome has not been definitively established yet. Dual antiplatelet therapy (aspirin and P2Y12 receptor inhibitors) reduces stent thrombosis and subsequent ischemic events. In turn, the presence of atrial fibrillation requires oral anticoagulation to prevent stroke and other thromboembolic complications. However, the combination of these two treatments, known as triple therapy, increases the risk of severe bleeding, with a negative prognostic impact. The use of direct anticoagulants, which reduce bleeding rates compared to warfarin, together with the maintenance of only one antiplatelet agent (P2Y12 inhibitors), known as dual therapy, may be a safer alternative in these patients. In this article, we reviewed several randomized studies comparing triple versus dual therapy, as well as meta-analyses with such studies, and the approaches suggested by the most recent guidelines, discussing the advantages and disadvantages of these treatments, in terms of safety and efficacy in this important and growing subgroup of patients.