Angina is a common symptom in hypertrophic cardiomyopathy and occurs in approximately 20% of patients. More than 50–75% of patients with HCM have myocardial ischemia on noninvasive testing. Of those patients with angina, approximately 25% have significant epicardial coronary artery disease. It is important to diagnose concomitant epicardial CAD in these patients as it is a predictor of increased mortality in HCM. The majority of HCM patients with myocardial ischemia do not have epicardial CAD, however. The proposed mechanisms of ischemia in the absence of epicardial CAD include increased oxygen demand, microvascular medial hypertrophy and dysfunction, and perturbations of cardiac-coronary coupling with reduction in systolic myocardial blood flow due to microvascular compression from a hypertrophic and hyperdynamic left ventricle and reduced diastolic myocardial blood flow due to blunting of diastolic suction secondary to impaired diastolic relaxation. Repetitive ischemic insults lead to myocardial injury and subsequent myocardial fibrosis. Myocardial ischemia in HCM patients is associated with increased mortality, ventricular tachycardia, left ventricular remodeling and dysfunction, and congestive heart failure. It is unknown whether the treatment of myocardial ischemia in HCM will influence outcomes.