Objective: To assess the efficacy of early pregnancy calcium and low dose of aspirin (LDA) in preventing preeclampsia and eclampsia in Blantyre, Malawi. Design: This was a double-blind cluster randomized controlled trial. Setting: Four urban health centers and Queen Elizabeth Central Hospital (QECH) as a referral site in Blantyre, Malawi. Population or sample: A total of 306 women at high-risk of preeclampsia were recruited. Methods: Women were assigned to LDA (150mg/day) or placebo from 12 to 16 weeks until 34 weeks of gestation in clusters. All women were additionally given calcium 1 gram/day. The intention to treat analysis and adherence analysis was conducted. Main outcome measure: The rate of preeclampsia. Results: A total of 39 women were lost to follow up and 1 withdrew consent. Data for 266 women was available for analysis. Overall preeclampsia occurred in 15.8% (42/266) and eclampsia in 2.3% (6/266) of all women. There was no statistically significant difference in the rate of preeclampsia between the LDA group 19% (26/135) and placebo group 14% (16/131) (adjusted OR 1.01 95%CI 0.34-3.04, p=0.135). No statistically significant difference was observed in the secondary maternal and neonatal outcomes. The overall adherence was 69%. Conclusion: Treatment with LDA and calcium in women at risk of preeclampsia resulted in no difference in the rate of preeclampsia, nor cesarean section rates, or important neonatal outcomes in Malawi. Funding: The study was funded by PEARLS at the Heart Research Institute, Sydney, Australia. It was registered by Pan African Clinical Trial Registry([http://www.pactr.org/](http://www.pactr.org/)) registration number PACTR202108825067735.