Reconstruction in the setting of prior breast irradiation is conventionally considered a higher-risk procedure. Limited data exist regarding nipple-sparing mastectomy in irradiated breasts, a higher-risk procedure in higher-risk patients. The authors identified and reviewed the records of 501 nipple-sparing mastectomy breasts at their institution from 2006 to 2013. Of 501 nipple-sparing mastectomy breasts, 26 were irradiated. The average time between radiation and mastectomy was 12 years. Reconstruction methods in the 26 breasts included tissue expander (n=14), microvascular free flap (n=8), direct implant (n=2), latissimus dorsi flap with implant (n=1), and rotational perforator flap (n=1). Rate of return to the operating room for mastectomy flap necrosis was 11.5 percent (three of 26). Nipple-areola complex complications included one complete necrosis (3.8 percent) and one partial necrosis (3.8 percent). Complications were compared between this subset of previously irradiated patients and the larger nipple-sparing mastectomy cohort. There was no significant difference in body mass index, but the irradiated group was significantly older (51 years versus 47.2 years; p=0.05). There was no statistically significant difference with regard to mastectomy flap necrosis (p=0.46), partial nipple-areola complex necrosis (p=1.00), complete nipple-areola complex necrosis (p=0.47), implant explantation (p=0.06), hematoma (p=1.00), seroma (p=1.00), or capsular contracture (p=1.00). In the largest study to date of nipple-sparing mastectomy in irradiated breasts, the authors demonstrate that implant-based and autologous reconstruction can be performed with complications comparable to those of the rest of their nipple-sparing mastectomy patients.