Left ventricular mass sometimes decreases during the treatment of hypertension. In a two-year open study, we investigated the ability of extended release (ER) felodipine (5 or 10 mg), plus chlorthalidone (25 mg), given once daily, to reduce left ventricular mass in 84 elderly patients with isolated systolic hypertension. Drug dosage was determined in an initial stepped-care titration phase lasting six weeks. Mean systolic blood pressure decreased after two years of treatment with 5 or 10 mg of felodipine (p < 0.001) and the left ventricular mass index decreased too (p < 0.0001). One or two weeks after withdrawal of therapies, blood pressure returned to pretreatment values. We concluded that left ventricular mass can be reduced in elderly patients with isolated systolic hypertension and ventricular hypertrophy who receive felodipine 5–10 mg once daily. This treatment was generally well tolerated.