Background: Chemoprevention with antiestrogens, tamoxifen and raloxifene, is under-utilized partly due to concerns regarding side effects such as uterine cancer and thromboembolism. Tamoxifen is indicated for women with ductal and lobular carcinoma in situ (DCIS/LCIS) and has a favorable risk-benefit ratio for high-risk women under age 50. For women 50 years and older, a Risk Benefit Index (RBI) developed by Freedman et al. takes into account a woman's age, race, breast cancer risk, and prior hysterectomy. We examined the correlation between RBI and chemoprevention uptake among high-risk women. Methods: From 2007 to 2013, new high-risk women seen at an urban, academic breast clinic were enrolled. Eligibility for chemoprevention included a 5-yr Gail risk≥1.67%, DCIS/LCIS, or BRCA mutation. RBI scores for tamoxifen and raloxifene based upon published algorithm tables were calculated for high-risk women ≥50 yrs and classified as strong/moderate evidence of benefits outweighing risks and benefits do not outweigh risks. Women with DCIS/LCIS/BRCA mutation and age<50 were excluded from the analysis. Results: Among 403 women enrolled, 311 (77%) were eligible for chemoprevention. Among women with DCIS/LCIS/BRCA mutation and age<50, 62% (124/201) and 31% (10/32) took an antiestrogen, respectively. Among 60 women with an RBI score, 82% had strong/moderate benefit; 33% took an antiestrogen with 65% in agreement with their RBI score. Among women who did not take an antiestrogen, 80% would have had a benefit to raloxifene or both. Conclusions: Among high-risk women who took an antiestrogen, the majority of treatment decisions were in agreement with their RBI score. Most women who refused an antiestrogen would have benefited. High-risk postmenopausal women now have the option of aromatase inhibitors, which may improve the risk-benefit profile for chemoprevention.