Abstract—Patients with hypertension exhibit impaired energetic coupling between the ventricle and the arterial system, leading to reduced cardiac mechanic efficiency and exercise capacity. We tested whether blood pressure normalization with current antihypertensive therapy can improve arterioventricular coupling. Eighteen hypertensive patients without other cardiovascular disease were examined before and after antihypertensive therapy. Transthoracic echocardiography was performed. Central aortic pressure waveforms, including end-systolic pressure, were derived from radial artery applanation tonometry. Afterload was increased with isometric handgrip exercise. Central aortic end-systolic pressure and ventricular volumes at rest and handgrip were used to calculate ventricular elastance, effective arterial elastance, arterioventricular coupling (effective arterial elastance/ventricular elastance), and mechanical efficiency. After 142±67 days, systolic blood pressure decreased from 150.9±14.6 to 119.8±9.2 mm Hg (P<0.00001), diastolic blood pressure from 85.9±14.8 to 68.8±8.4 mm Hg (P=0.00002), and cardiac output from 5.8±1.7 to 4.9±1.8 L/min (P=0.03). Resting left ventricular end-systolic volume, ejection fraction, and septal thickness did not change. Ventricular elastance increased from 1.7±1.0 to 3.2±1.4 mm Hg/mL (P=0.00002), whereas effective arterial elastance decreased from 1.4±0.5 to 1.2±0.4 mm Hg/mL (P=0.02). Effective arterial elastance/ventricular elastance decreased in all patients, from 1.1±0.8 to 0.4±0.2 (P=0.0002). Efficiency improved at rest (72.9±5.8% versus 83.5±5.7%; P<0.00001) and during handgrip (63.5±7.8% versus 78.9±7.1%; P<0.00001). In hypertensive patients, optimal brachial and central blood pressure reduction shifts arterioventricular coupling from cardiac output maximization to ventricular mechanical efficiency optimization. This occurs before significant changes in ventricular geometry and may be responsible for early clinical improvements.