Purpose Women with Li–Fraumeni Syndrome (LFS) often consider risk-reducing mastectomy (RRM) due to extremely high risk of breast cancer at early ages. Data on uptake of RRM in LFS are scarce, and are inferred from experience in women with pathogenic variants (PVs) in BRCA1/2 , despite differences in cancer risks. This study evaluated RRM uptake in a cohort of women with LFS. Methods Women ( n  = 205) with LFS enrolled in NCI’s LFS study reported lifetime cancer diagnoses and mastectomies and completed questionnaires regarding reproductive history, cancer worry and risk perceptions. A subset of women participating in an annual cancer screening study received counseling regarding RRM. Results 65% ( n  = 71) of women diagnosed with presumed unilateral breast cancer ( n  = 109) underwent contralateral RRM over their lifetime. Nearly half (49%, n  = 25) of the women who did not complete contralateral RRM within one year of their breast cancer diagnosis ( n  = 51) developed contralateral breast cancer (median interval = 6 years). Only 18.5% ( n  = 15) of women without breast cancer history ( n  = 81) underwent bilateral RRM. Median age at bilateral RRM of 39 years was sub-optimal for breast cancer risk reduction. Contralateral RRM was associated with early genetic diagnosis, participation in the screening study, and fewer prior cancers. Bilateral RRM uptake was associated with having had children, having breastfed, and high cancer worry. Conclusion Uptake of contralateral RRM is high in women with LFS. The frequency of contralateral breast cancer necessitates active discussion of benefits of contralateral RRM and counseling regarding bilateral RRM should be tailored to the early age at risk of breast cancer onset in LFS. There is a need for research into the survival and long-term benefits of RRM in LFS.