Abstract--Aspirin is a potent antioxidative agent that reduces vascular production of superoxide, prevents angiotensin II-induced hypertension, and induces NO release. Low-dose aspirin administered at bedtime, but not on awakening, has also been shown to reduce blood pressure, possibly enhancing the nocturnal trough in NO production. Because endothelium-dependent vasodilation is blunted through a decrease in NO release in non-dipper compared with dipper patients, we compared the administration time-dependent influence of aspirin on ambulatory blood pressure in dipper and non-dipper hypertensive subjects. We studied 257 patients with mild hypertension (98 men and 159 women), 44.6±12.5 years of age, randomly assigned to receive 100 mg per day of aspirin either on awakening or at bedtime. Ambulatory blood pressure was measured for 48 hours at baseline and after 3 months of intervention. Blood pressure was slightly elevated after aspirin on awakening (increase of 1.5/1.0 mm Hg in the 24-hour mean of systolic/diastolic blood pressure; P<0.028). A highly significant blood pressure reduction was observed in patients who received aspirin at bedtime (decrease of 7.2/4.9 mm Hg in systolic/diastolic blood pressure; P<0.001). The reduction in nocturnal blood pressure mean was double in non-dippers (11.0/7.1 mm Hg) compared with dippers (5.5/3.3 mm Hg; P<0.001). This prospective trial corroborates the significant administration time-dependent effect of low-dose aspirin on blood pressure, mainly in non-dipper hypertensive patients. The timed administration of low-dose aspirin could thus provide a valuable approach, beyond prevention of cardiovascular disease, in the blood pressure control of patients with mild hypertension. (Hypertension. 2005;46[part 2]:1-9.)