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Nipple-sparing techniques have improved the aesthetics of reconstruction following mastectomy, but nipple necrosis complicates up to 37% of procedures, distressing patients, delaying adjuvant therapy, and compromising outcomes. No method reliably detects nipple necrosis better than clinical assessment of tissue perfusion. We prospectively assessed the accuracy of intraoperative indocyanine green laser angiography to predict nipple necrosis.Twenty consecutive women undergoing immediate tissue expander breast reconstruction following 32 nipple-sparing mastectomies underwent indocyanine green fluorescence imaging to assess nipple perfusion immediately before and after intraoperative tissue expansion. Imaging findings were correlated with postoperative nipple viability.Among the 32 nipple-sparing mastectomies (8 unilateral, 12 bilateral) in 20 women (mean age, 48 years), partial or full-thickness necrotic changes developed in 3 breasts of 2 patients (10%). Imaging identified impaired perfusion and predicted necrosis in these cases.In this initial series, intraoperative indocyanine green laser angiography correctly identified patients who developed nipple necrosis during mastectomy and tissue expander breast reconstruction.