BACKGROUND Drugs with negative inotropic effect are widely used to decrease obstruction in hypertrophic cardiomyopathy (HCM). However, the mechanism of therapeutic benefit has not been studied. METHODS AND RESULTS We used M-mode, two-dimensional, and pulsed Doppler echocardiography to study 11 patients with obstructive HCM before and after medical elimination of left ventricular outflow tract obstruction. We measured 148 digitized pulsed Doppler tracings recorded in the left ventricular cavity 2.5 cm apical of the mitral valve. Successful treatment slowed average acceleration of left ventricular ejection by 34% (P=.001). Mean time to peak velocity in the left ventricle was prolonged 31% (P=.001). Mean time to an ejection velocity of 60 cm/s was prolonged 91% (P=.001). Before treatment, left ventricular ejection velocity peaked in the first half of systole; after successful treatment, it peaked in the second half (P=.001). In contrast, after treatment, we found no change in peak left ventricular ejection velocity. We also found no change in the distance between the mitral coaptation point and the septum, as measured in two planes, indicating no treatment-induced alteration of this anatomic relationship. CONCLUSIONS Medical treatment eliminates mitral-septal contact and obstruction by decreasing left ventricular ejection acceleration. By slowing acceleration, treatment reduces the hydrodynamic force on the protruding mitral leaflet and delays mitral-septal contact. This, in turn, results in a lower final pressure gradient.