ObjectiveThe aim of this study was to compare the roles of low-dose aspirin and folic acid in the prevention of preeclampsia among high-risk pregnant women with high resistance in the uterine artery documented by uterine artery Doppler waveforms at 22-24 weeks of gestation. Study designThis was a prospective randomized-controlled trial. SettingThis study was carried out at the Department of Obstetrics and Gynecology, Cairo University (Cairo, Egypt). Patients and methodsA total of 1262 pregnant women at high risk of developing preeclampsia were screened at 22-24 weeks of gestation with uterine artery Doppler. Two hundred and ten participants were divided randomly into three groups. Group 1 received oral aspirin 75 mg/day, group 2 received oral folic acid 1 mg/day, and group 3 was the control group. The incidence of preeclampsia was recorded in each group and the results of the groups were compared. ResultsThe incidence of preeclampsia was 33% in the aspirin group, 51% in the folic acid group, and 56% in the control group. Comparison of the aspirin group with the control group showed a significant reduction in preeclampsia in the aspirin group (P = 0.01). Comparison between the folic acid group and the control group showed a nonsignificant reduction in preeclampsia in the folic acid group (P = 0.753). Comparison between the aspirin group and the folic acid group showed a significant reduction of preeclampsia in the aspirin group (P = 0.04). ConclusionIn high-risk patients with high resistance in the uterine circulation, aspirin is potentially effective in reducing the incidence of preeclampsia whereas folic acid is not.