PURPOSE: We conducted a secondary analysis of a randomized, placebo-controlled trial to test if hormone therapy (HT) altered the risk of open-angle glaucoma (OAG), and if the risk reduction varied by race. DESIGN: Secondary analysis of randomized controlled trial data. METHODS: We linked Medicare claims data to 25 535 women in the Women's Health Initiative. Women without a uterus were randomized to receive either oral conjugated equine estrogens (CEE 0.625 mg/day) or placebo, and women with a uterus received oral CEE and medroxyprogesterone acetate (CEE 0.625 mg/day + MPA 2.5 mg/day) or placebo. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence interval. RESULTS: After exclusion of women with prevalent glaucoma or without claims for eye care provider visits, the final analysis included 8102 women (mean age = 68.5 ± 4.8 years). The OAG incidence was 7.6% (mean follow-up = 11.5 ± 5.2 years; mean HT duration = 4.4 ± 2.3 years). Increased age (P trend = .01) and African-American race (HR = 2.69, 95% CI = 2.13-3.42; white as a reference) were significant risk factors for incident OAG. We found no overall benefit of HT in reducing incident OAG (HR = 1.01, 95% CI = 0.79-1.29 in the CEE trial, and HR = 1.05, 95% CI = 0.85-1.29 in the CEE + MPA trial). However, race modified the relationship between CEE use and OAG risk (P interaction = .01), and risk was reduced in African-American women treated with CEE (HR = 0.49, 95% CI = 0.27-0.88), compared to placebo. Race did not modify the relation between CEE + MPA use and OAG risk (P interaction = .68). CONCLUSIONS: Analysis suggests that HT containing estrogen, but not a combination of estrogen and progesterone, reduces the risk of incident OAG among African-American women. Further investigation is needed.