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 ill the second half(P=.001). In contrast, after treatment, we found no change in peak left ventricular-ejection velocity. We also found Ilo 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 leaner and delays mitral-septal contact. This, in turn, results in a lower final pressure gradient.