In a double-blind, randomized, multicenter study the antihypertensive efficacy of cilazapril 5.0 and 2.5 mg once daily vs. placebo was examined on 180 ambulatory hypertensive subjects with supine diastolic office blood pressure (OBP) 3 ≥ 95 and ≤ 115 mm Hg: a 4-week, single-blind, placebo period was followed by a 4-week double-blind treatment period. At the beginning and end of the latter, OBP measurements and ambulatory 24-h BP monitoring (ABPM) were both carried out on two different days (3 ± 1), whereby each time two 24-h BP recordings were made using SpaceLabs 90202. Measurements were made every 30 min, and actual waking and sleeping phase evaluation was done using diary entries. White coat hypertensive patients were excluded by the ambulatory BP (ABP) inclusion criterion: mean diastolic 24-h BP ≥ 85 mm Hg, or frequency of measurements > 90 mm Hg 5 ≥ 35%. One-hundred eighty patients were included in the study. Safety was evaluated in 170 of these patients, and efficacy on OBP in 162. Twenty-four-hour BP recordings that were amenable to analysis were available in the case of 146 patients (average age 56 ± 10 years, 56 women, 90 men). The results of the main target variable for OBP, namely responder rates, were in the three treatment groups: placebo, 39.6%; cilazapril 2.5 mg, 55.6%; and cilazapril 5.0 mg, 65.5%. All three treatment groups revealed a statistically significant effect (p < 0.001) on the reduction of mean BP values: placebo from 161.6/102.2 to 149.4/94.7 mm Hg, cilazapril 2.5 mg from 162.9/102.1 to 149.7/92.0 mm Hg, and cilazapril 5.0 mg from 158.4/100.6 to 145.6/90.5 mm Hg. In contrast to OBP data, the analysis of the 24-h ABP profile showed a significant global antihypertensive effect on systolic and diastolic mean values only in the case of the two cilazapril dosages (p < 0.001). The drop in 24-h mean values was as follows: placebo from 148.3/91.7 to 146.1/90.1, cilazapril 2.5 mg from 151.0/93.3 to 143.6/88.9, cilazapril 5.0 mg from 148.0/92.2 to 140.8/86.1. Analysis of the placebo effect using OBP measurement and ABPM led to completely opposing conclusions. In OBP measurement, a highly significant antihypertensive 24-h trough effect is simulated. In 24-h BP, the placebo effect is slight and restricted to a limited time interval (approximately 8 h) during the active waking phase. Both cilazapril groups had equipotent antihypertensive effects on systolic BP but distinctly dose dependent effects on diastolic BP. Both dosages demonstrated a continuous BP control, especially during the critical early morning waking-getting-up phase. Cilazapril 2.5 and 5.0 mg once daily was well tolerated.