Several studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several CCB, including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. A previous trial on a very small number of patients (n=10) concluded that the time of administration of 30 mg/d nifedipine gastrointestinal therapeutic system (GITS) has no impact on therapeutic efficacy [Clin Investig. 1994;72:864–869]. We investigated the antihypertensive efficacy and effects on the circadian BP pattern of nifedipine GITS in doses of 30 and 60 mg/d administered at different times according to the rest-activity cycle of each patient. We studied 80 previously untreated patients with grade 1–2 essential hypertension (36 men and 44 women), 52.1±10.7 years of age, randomly assigned to receive nifedipine GITS (30 mg/d) as a monotherapy for 8 weeks either upon awakening or at bedtime. Uncontrolled patients were titrated to receive 60 mg/d nifedipine GITS for another 8 weeks. BP was measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 hours before and after every 8 weeks of therapy. The BP reduction after 8 weeks of therapy with the lower dose of 30 mg/d was slightly but not significantly larger after bedtime dosing (10.3 and 6.5 mm Hg reduction in the 24-hour mean of systolic and diastolic BP after nifedipine GITS on awakening; 12.0 and 7.2 mm Hg after bedtime dosing). In non-responders to this low dose, the efficacy of 60 mg/d nifedipine GITS was markedly larger after bedtime dosing (16.0 and 9.3 mm Hg in systolic and diastolic BP, as compared to 8.4 and 4.0 mm Hg after morning dosing; P<0.03). Moreover, bedtime administration of nifedipine GITS reduced the incidence of edema by 91% and the total number of secondary effects by 74% as compared to morning dosing (P=0.02). Independently of the time of administration, a single daily dose of 30 mg/d of nifedipine GITS efficiently reduces BP for the whole 24 hours of the day. The added efficacy with 30 mg/d, the marked benefits with 60 mg/d, and the safety profile of bedtime administration of nifedipine GITS should be taken into account when prescribing this CCB in the treatment of essential hypertension.