Recent studies have shown no influence of aspirin (ASA) on blood pressure (BP) in hypertensive patients under antihypertensive therapy, yet little if any attention has been paid so far in clinical trials to potential circadian-time dependencies in effects. However, an administration-time dependent effect of low-dose ASA on BP has been previously documented in normotensive volunteers, in patients with untreated mild hypertension, and in pregnant women at high risk for preeclampsia [Hermida et al. Hypertension. 2003;41:in press]. In keeping with these findings, the present study investigated the influence of ASA on BP in previously untreated hypertensive patients, who received ASA at different times of the day according to their rest-activity cycle. We studied 147 patients with mild hypertension (57 men and 90 women), 43.0±12.1 (mean±SD) years of age, divided in 3 groups: non-pharmacological hygienic-dietary recommendations (HDR); the same HDR and ASA (100 mg/day) on awakening; or HDR and ASA before bedtime. BP and heart rate (HR) were measured every 20 minutes during the day (07:00 to 23:00 hours) and every 30 minutes at night for 48 consecutive hours before and after 3 months of intervention. The circadian pattern of BP in each group was established by population multiple-component analysis [Fernandez & Hermida. Chronobiol Int. 1998;15:191-204]. After 3 months of non-pharmacological intervention, there was a small and non-significant reduction of BP (1.1 and 1.0 mm Hg for systolic and diastolic BP; P>0.341). There was no effect of ASA on BP when given on awakening (P=0.229). A BP reduction was, however, highly signif-icant when ASA was given before bedtime (decrease of 7.1 and 4.4 mm Hg in systolic and diastolic BP, respectively; P<0.001). There was no significant change in HR in any group. This trial corroborates the highly significant administration-time dependent effect of low-dose ASA on BP in untreated patients with mild hypertension. Results indicate that the timed administration of low-dose ASA with respect to the rest-activity cycle of each patient could provide a valuable approach not just for the secondary prevention of cardiovascular disease, but also in the added BP control of patients with mild essential hypertension and poor compliance with hygienic and/or dietary recommendations.