Abstract Purpose: To compare phenotype features and survival of triple-negative breast cancers (TNBC) versus non-TNBCs detected during a multimodal annual screening of high-risk women. Experimental Design: Analysis of data from asymptomatic high-risk women diagnosed with invasive breast cancer during the HIBCRIT-1 study with median 9.7-year follow-up. Results: Of 501 enrolled women with BRCA1/2 mutation or strong family history (SFH), 44 were diagnosed with invasive breast cancers: 20 BRCA1 (45%), 9 BRCA2 (21%), 15 SFH (34%). Magnetic resonance imaging (MRI) sensitivity (90%) outperformed that of mammography (43%, P < 0.001) and ultrasonography (61%, P = 0.004). The 44 cases (41 screen-detected; 3 BRCA1-associated interval TNBCs) comprised 14 TNBCs (32%) and 30 non-TNBCs (68%), without significant differences for age at diagnosis, menopausal status, prophylactic oophorectomy, or previous breast cancer. Of 14 TNBC patients, 11 (79%) were BRCA1; of the 20 BRCA1 patients, 11 (55%) had TNBC; and of 15 SFH patients, 14 (93%) had non-TNBCs (P = 0.007). Invasive ductal carcinomas (IDC) were 86% for TNBCs versus 43% for non-TNBCs (P = 0.010), G3 IDCs 71% versus 23% (P = 0.006), size 16 ± 5 mm versus 12 ± 6 mm (P = 0.007). TNBC patients had more frequent ipsilateral mastectomy (79% vs. 43% for non-TNBCs, P = 0.050), contralateral prophylactic mastectomy (43% vs. 10%, P = 0.019), and adjuvant chemotherapy (100% vs. 44%, P < 0.001). The 5-year overall survival was 86% ± 9% for TNBCs versus 93% ± 5% (P = 0.946) for non-TNBCs; 5-year disease-free survival was 77% ± 12% versus 76% ± 8% (P = 0.216). Conclusions: In high-risk women, by combining an MRI-including annual screening with adequate treatment, the usual reported gap in outcome between TNBCs and non-TNBCs could be reduced. Clin Cancer Res; 22(4); 895–904. ©2015 AACR.