OBJECTIVE To evaluate the antihypertensive effects and tolerability of a sustained release preparation of nicardipine (NIC SR), a dihydropyridine calcium channel antagonist. METHODS After at least 1 week without receiving antihypertensive medications and 2 weeks of single-blind placebo treatment, the patients were randomized to receive in a double-blind fashion, either placebo or NIC SR 30, 45, or 60 mg twice daily at 12-h intervals for 12 weeks. Supine and standing blood pressure were measured in all patients and 24-h ambulatory blood pressure monitoring was performed in a subset of 75 patients at baseline during treatment with single-blind placebo and during the double-blind treatment period. METHODS Academic and private hypertension research clinics. METHODS Two hundred sixty-four patients with supine diastolic blood pressures of 95 to 114 mm Hg, ranging in age from 22 to 75 years and in weight from 50 to 137 kg, approximately evenly divided by gender; one third were black. RESULTS In comparison with placebo, all doses of NIC SR significantly reduced systolic and diastolic blood pressures, with a trend toward greater effects from 45 to 60 mg twice daily than with 30 mg twice daily. At all doses, reduction of blood pressure from baseline levels was fully apparent within the first 2 weeks of therapy and was maintained throughout the remaining 10 weeks of the trial. Ambulatory blood pressure monitoring demonstrated that the antihypertensive effect was maintained throughout the dosing interval. Adverse effects were primarily extensions of pharmacologic activity (eg, pedal edema, flushing). Six percent of the placebo group and 10 percent of the combined NIC SR groups experienced at least one adverse event that was judged to be probably related to therapy. Withdrawals due to unacceptably high blood pressure totaled 5 percent of the combined NIC SR groups and 25 percent of the placebo group. CONCLUSIONS Sustained-release nicardipine at a dose of 30 to 60 mg every 12 h provided effective and generally well-tolerated antihypertensive control throughout the day in most patients with mild-to-moderate essential hypertension.