Postoperative complications after total skin-sparing mastectomy and expander-implant reconstruction can negatively impact outcomes, particularly in the setting of postmastectomy radiation therapy. The authors studied whether rates of ischemic complications after postmastectomy radiation therapy are impacted by the total skin-sparing mastectomy incision.The authors queried a prospectively collected database of patients undergoing total skin-sparing mastectomy and immediate two-stage expander-implant reconstruction. Their hypothesis was that, in the setting of radiation therapy, patients with inframammary incisions would be more likely to develop ischemic complications than those without incisions on the dependent portion of the breast. We divided our patient cohort into two groups, those with inframammary incisions and those with other incisions, and then analyzed the proportion that received radiation therapy.Of 756 cases included in the analysis, 91 (12 percent) received postmastectomy radiation therapy, 62 (68.1 percent) with inframammary incisions and 29 (31.9 percent) with other incisions. Mean follow-up was 3.1 years. Rates of mastectomy skin flap necrosis (3.2 percent versus 6.9 percent, p=0.4) following radiation therapy were not significantly higher in the inframammary group. However, breakdown of the total skin-sparing mastectomy incision was twice as likely in the inframammary group (21 percent versus 10.3 percent, p=0.2) and was more likely to lead to subsequent implant removal when incisional breakdown occurred (77 percent versus 0 percent, p=0.03).Total skin-sparing mastectomy incision type may impact rates of incisional breakdown and implant loss following postmastectomy radiation therapy, with higher rates seen with inframammary incisions. Multiple factors, including breast size, breast ptosis, and likelihood of radiation therapy, should be considered in determining optimal incision.Therapeutic, III.