Acute coronary syndrome and atrial fibrillation are both common and can occur in the same patient. Combination therapy with dual antiplatelet therapy and oral anticoagulation increases risk of bleeding. Where the two conditions coexist, careful consideration is needed to determine the optimal antithrombotic treatment to reduce the risks of future ischaemic events associated with both conditions. Choices can be made in intraprocedural anticoagulation, type and dosing of oral anticoagulant, duration of combination therapy, and selection of P2Y12 inhibitor including genetic testing. This review article provides an overview of the available evidence to support clinicians in finding the delicate balance between antithrombotic efficacy and bleeding risk in patients with acute coronary syndrome and atrial fibrillation.