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Wellens syndrome is a pattern of electrocardiographic (ECG) changes in the context of unstable angina characterized with deep inverted T-waves or biphasic T-waves in the precordial leads. These specific ECG changes are highly suggestive of stenosis in the left anterior descending artery (LAD), which can result in acute myocardial infarction, left ventricular dysfunction, or death. Human immunodeficiency virus (HIV) infection is known as an independent risk factor for the cardiovascular disease.The first case is a 61-year-old African American female with a history of HIV infection who presented with chest pain for 8 h. Electrocardiogram (ECG) showed deep T-waves inversions in leads V3–V6. Emergent cardiac catheterization showed 99% stenosis in the mid-LAD and a drug-eluting stent (DES) was subsequently placed. The second case is a 49-year-old African American female with a medical history of type 2 diabetes mellitus, HIV, active cigarettes smoker admitted for intermittent substernal chest pain of 1-day duration. ECG showed biphasic T-wave in V2 and deep T-waves inversion in V3–V4, coronary angiography showed 95% stenosis in the proximal LAD and a DES was placed.Wellens syndrome has characteristic ECG changes that indicates LAD stenosis. Early recognition of this syndrome, especially in HIV-infected patients who are high risk for cardiovascular disease, will help to avoid impending myocardial infarction.