The aim of this study was to assess whether left ventricular (LV) cavity size relates to functional impairment and syncope in patients with hypertrophic cardiomyopathy (HC). LV diastolic dysfunction influences functional limitation in HC. A reduced LV end-diastolic dimension may underlie impaired diastolic properties and be implicated in hemodynamic syncope. Eighty-two consecutive patients with HC (off drugs, in sinus rhythm) underwent echocardiography to measure LV end-diastolic dimension in the short-axis view (indexed to the body surface area) and radionuclide angiography (n = 50) to calculate peak filling rate (normalized to stroke counts/s). Patients in New York Heart Association functional classes II to IV had smaller LV end-diastolic dimension (23.2 +/- 2.6 vs 25.5 +/- 2.5 mm/M2, p = 0.0001) and lower peak filling rate (4.3 +/- 1.4 vs 5.1 +/- 1.3 stroke counts/s, p = 0.036) than those in New York Heart Association class I. LV end-diastolic diameter was correlated to peak filling rate (r = 0.37; p = 0.008). The most potent predictors of functional limitation were LV end-diastolic dimension (relative risk [RR] 0.63, confidence interval [CI] 0.45 to 0.88; p = 0.008), age (RR 1.09, CI 1.03 to 1.17; p = 0.003), and LV thickness score (RR 1.08, CI 1.02 to 1.13; p = 0.003). LV cavity size was smaller in patients with functional limitation irrespective of obstruction and hypertrophy. Patients with differed from those without a history of syncope for a smaller LV end-diastolic dimension (23.2 +/- 2.5 vs 25.0 +/- 2.7 mm/M2, p = 0.008), which was the only independent predictor of syncope (RR 0.77, CI 0.63 to 0.95; p = 0.013). Thus, a small LV cavity size is associated with functional limitation and history of syncope in HC.