In-vitro and in-vivo evidence has supported the role of angiotensin II blockade in reducing leiomyoma cell proliferation and growth. However, no population-based study to date has investigated this potential association.To determine if prior Angiotensin-Converting Enzyme inhibitor (ACEi) use is associated with reduced odds of leiomyoma development.A nested case-control study.The population was assembled from the Truven Health Marketscan® Research Database, which includes private health insurance claims from January 1 st, 2012 to December 31 st, 2017.We included (n=353,917) women aged 18-65 with hypertension. Cases (n=13,108) with a leiomyoma diagnosis were matched to controls (n=340,808) with no such diagnosis at a 1:26 ratio by age and region of origin within the United States.Prior use of ACEi was determined from outpatient drug claims.Leiomyoma development was indicated by a first time diagnosis code.Women on an ACEi experienced a 31.8% reduced odds of developing clinically recognized leiomyoma compared to non-users (OR 0.68, 95% CI 0.65-0.72). This association was significant for each age group: 30-39 (OR 0.86, 95% CI 0.74-0.99), 40-49 (OR 0.71, 95% CI 0.66-0.76), 50-59 (OR 0.63, 95% CI 0.58-0.69) and 60-65 years old (OR 0.58, 95% CI 0.50-0.69). Of the ACEi's, Lisinopril (OR 0.67, 95% CI 0.64-0.71), Quinapril (OR 0.62, 95% CI 0.41-0.92) and Ramipril (OR 0.35, 95% CI 0.23-0.50) demonstrated a significant association with reduced leiomyoma incidence.ACEi use is associated with reduced odds of developing clinically recognized leiomyoma in adult hypertensive women.