question: Objective: Numerous studies have evaluated the efficacy and safety of low dose aspirin for preeclampsia prevention in high risk women. Most studies were European based demonstrating efficacy and safety with aspirin 150 mg, with studies in the United States supporting aspirin 81 mg for preeclampsia prevention. There is limited data from the United States evaluating aspirin 162 mg;the aim of this study was to examine the efficacy and safety of aspirin 162 mg vs 81 mg vs no aspirin for preeclampsia prevention. Study Design: A retrospective cohort study was performed at Henry Ford Health System (HFHS) between 2013 and 2020. The ‘no aspirin’ group was composed of women who met high risk criteria prior to October 2015, when aspirin was implemented at HFHS. The ‘aspirin 81 mg’ and ‘aspirin 162 mg’ groups were composed of women who met high risk criteria prophylaxed with the respective aspirin doses after October 2015. Exclusion was made for women with bleeding disorders, sensitivity to aspirin, and covid-19 infection (as applicable). Results: A total of 2,266 women met high risk criteria prior to October 2015 and received no treatment. A total of 944 women received aspirin 81 mg and 387 women received aspirin 162 mg. 322 women (14.2%) without treatment developed preeclampsia, compared to 134 women (14.2%) in the aspirin 81 mg group and 39 (10.1%) in the aspirin 162 mg group. The difference in preeclampsia rates between aspirin 81 mg and aspirin 162 mg was statistically significant (p = 0.043). The risks for postpartum hemorrhage, postpartum hematoma, and intraventricular hemorrhage of the newborn were not statistically different between women in the aspirin 162 mg group compared to the aspirin 81 mg group (p >0.05). Conclusion: We found a 29% reduction in the rate of preeclampsia for high risk women with aspirin 162 mg vs aspirin 81 mg without an increased risk for bleeding. Our study demonstrates that aspirin 162 mg should be recommended for preeclampsia prophylaxis in high risk women. Further studies by other groups are needed to confirm these findings.