This study assessed once-daily sustained-release (o.d. SR) diltiazem in essential hypertension; 158 patients with supine diastolic blood pressures (BP) of 95-115 mm Hg were randomized to 200 mg diltiazem or placebo, then optimally titrated, at 2-week intervals, to 200, 300 or 400 mg to achieve supine diastolic BP < 90 mm Hg or a ≧ 10 mm Hg fall from baseline. BP was measured at trough level, 24 h after dosing. After 2 weeks at the dose of 200 mg, supine diastolic BP was significantly reduced (from 101 to 92 mm Hg) compared with placebo (from 101 to 98 mm Hg; p < 0.001), and yielded 57% of responders with diltiazem against 22% with placebo (p < 0.001). Titration allowed supine diastolic BP normalization with diltiazem (88 mm Hg) compared with placebo (93 mm Hg; p < 0.001) and yielded 78% of responders with diltiazem against 37% with placebo (p < 0.01). The safety profile was similar to placebo. 200 and 300 mg o.d. SR diltiazem formulations enable safe and close regimen adjustments in mild-to-moderate essential hypertension.