The course of obstructive hypertrophic cardiomyopathy is infrequently punctuated by an acute episode of left ventricular ballooning that presents clinically like an acute coronary syndrome with typical chest pain, collapse, or heart failure. Coronary angiography shows no significant stenoses. Such patients differ from patients with acute neurohumoral Takotsubo syndrome because their LV ballooning is caused by systolic anterior motion of the mitral valve, mitral-septal contact, and severe unrelenting outflow obstruction that causes severe afterload mismatch and supply-demand ischemia. Unselected patients who present to the emergency department with LV ballooning are found to have obstructive HCM as the cause about a quarter of the time. Sources of diagnostic ambiguity and confusion between ballooning caused by obstructive HCM and neurohumoral Takotsubo syndrome are discussed in this chapter. Treatment differences are discussed as well.