In hypertrophic cardiomyopathy (HC), an important subgroup of patients develop progressive and disabling symptoms that are related to heart failure and death. Although a direct relation has been demonstrated between left ventricular (LV) wall thickness and likelihood of sudden and unexpected death (usually in patients who are asymptomatic or mildly symptomatic), it is unresolved whether magnitude of hypertrophy is similarly associated with severity of heart failure. To determine the relation of LV wall thickness to heart failure symptoms in HC, 700 consecutive patients who had HC were assessed by 2-dimensional echocardiography. The relation between maximum level of heart failure symptoms by New York Heart Association functional class and maximum LV wall thickness was not linear but rather parabolic. Therefore, marked symptoms were most commonly associated with moderate degrees of LV hypertrophy (wall thickness 16 to 24 mm; 27%) but less frequently with extreme hypertrophy (>/=30 mm 13%) or mild hypertrophy (</=15 mm; 19%, p = 0.0001). Mean New York Heart Association functional class showed a similar pattern with respect to moderate hypertrophy (1.9 +/- 0.8), mild hypertrophy (1.6 +/- 0.9), and extreme hypertrophy (1.6 +/- 0.7, p = 0.005). Multivariable regression analysis showed the parabolic relation between heart failure symptoms and magnitude of LV hypertrophy to be independent of other hypertrophic cardiomyopathy related clinical variables. In conclusion, no direct relation was evident between symptoms of heart failure and magnitude of LV wall thickness, with implications for the natural history of HC.