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Dual antiplatelet therapy, consisting of aspirin and a P2Y12 receptor antagonist, has been the cornerstone of management in those undergoing percutaneous coronary intervention, reducing stent thromboses and cardiovascular events. Given the pivotal role of aspirin in cardiovascular disease management, patients with aspirin hypersensitivity pose complex clinical challenges. Allergy to aspirin is reported in 1.5-2.6% of patients presenting with cardiac disease. Identification of the subtype of aspirin hypersensitivity will determine suitability for aspirin desensitization, dictate choice of desensitization protocol and inform risk management. Aspirin desensitization is an effective and viable clinical strategy, although it remains underutilised in clinical practice. Collaboration between cardiologists and immunologists should be strongly encouraged to facilitate optimal management of such patients. This review describes the complexity of managing patients with aspirin hypersensitivity in cardiac disease, the indications and risks of aspirin desensitization, and the approach to management of the minority of patients who are unsuitable for desensitization.