This study prospectively investigates the potential influence of low-dose aspirin on blood pressure in pregnant women who were at a higher risk of developing preeclampsia than that of the general obstetric population and who received aspirin at different times of the day according to their rest-activity cycle. A double-blind, randomized, controlled trial was conducted in 341 pregnant women (181 primipara) randomly assigned to 1 of 6 possible groups according to treatment (either placebo or aspirin, 100 mg/day, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Blood pressure was automatically monitored for 48 consecutive hours every 4 weeks from the day of recruitment until delivery, as well as at puerperium. There was no effect of aspirin on blood pressure at time 1 (compared with placebo). A blood pressure reduction was highly statistically significant when aspirin was given at time 2 and, to a greater extent, at time 3 (mean reductions of 9.7/6.5 mm Hg in 24-hour mean for systolic/diastolic blood pressure at the time of delivery as compared with placebo given at bedtime). Differences in blood pressure among women receiving aspirin at different circadian times disappeared at puerperium (P>0.096). Results indicate a highly significant effect of aspirin on blood pressure that is markedly dependent on the time of aspirin administration with respect to the rest-activity cycle. Timed use of aspirin at low dose effectively contributes to blood pressure control in women at high risk for preeclampsia.