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Nipple-sparing mastectomy (NSM) offers superior cosmetic outcomes and has been gaining wide acceptance; however, its role among patients with BRCA mutations remains controversial.To report on the oncologic safety of NSM and provide evidence-based data to patients and health care professionals regarding preservation of the nipple-areolar complex during a risk-reducing mastectomy in a population with BRCA mutations.We retrospectively reviewed the outcomes of 9 institutions’ experience with prophylactic NSM from 1968 to 2013 in a cohort of patients with BRCA mutations. Patients with breast cancer were included if they underwent contralateral risk-reducing mastectomy; however, only the prophylactic side was considered in the analysis. Patients found to have an occult primary breast cancer at the time of risk-reducing mastectomy, those having variant(s) of unknown significance, and those undergoing free nipple grafts were excluded.The primary outcome measure was development of a new breast cancer after risk-reducing NSM. Three reference data sources were used to model the expected number of events, and this was compared with our observed number of events.A total of 548 risk-reducing NSMs in 346 patients were performed at 9 institutions. The median age at NSM was 41 years (interquartile range, 34.5-47.5 years). Bilateral prophylactic NSMs were performed in 202 patients (58.4%), and 144 patients (41.6%) underwent a unilateral risk-reducing NSM secondary to cancer in the contralateral breast. Overall, 201 patients with BRCA1 mutations and 145 with BRCA2 mutations were included. With median and mean follow-up of 34 and 56 months, respectively, no ipsilateral breast cancers occurred after prophylactic NSM. Breast cancer did not develop in any patients undergoing bilateral risk-reducing NSMs. Using risk models for BRCA1/2 mutation carriers, approximately 22 new primary breast cancers were expected without prophylactic NSM. Prophylactic NSM resulted in a significant reduction in breast cancer events (test of observed vs expected events, P < .001).Nipple-sparing mastectomies are highly preventive against breast cancer in a BRCA population. Although the follow-up remains relatively short, NSM should be offered as a breast cancer risk–reducing strategy to appropriate patients with BRCA mutations.