© 2017 The Author. Although the inverse association between hysterectomy and epithelial ovarian cancer (EOC) was considered well established, investigators in recent studies including women diagnosed after 2000 have observed modest increases in risk. Most studies have been conducted in white women with little representation of African-American women. We examined the relationship between premenopausal hysterectomy and EOC in African-American women and explored whether hormone therapy (HT) modified this association in 614 cases and 743 controls enrolled in the African American Cancer Epidemiology Study (2010-2015). Premenopausal hysterectomy was inversely associated with the odds of EOC (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.56, 1.01). Qualitative interaction by estrogen-only HT was present; among never users of estrogen-only HT, premenopausal hysterectomy was associated with a significantly decreased odds of EOC (OR = 0.65, 95% CI: 0.46, 0.92), whereas among users of estrogen-only HT, a positive association was observed (OR = 1.71, 95% CI: 0.76, 3.84). In a population of African-American women diagnosed after 2000, our overall results are consistent with the inverse association observed in the era before 2000, yet the effect modification by HT suggests that HT use among women who have had hysterectomies may negate the protective effects of hysterectomy on EOC, creating the appearance of a null or slightly increased risk.