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Tissue expander placement is a mainstay of reconstructive surgery in the post-mastectomy patient. Necrosis of the native breast tissue is one of the most significant concerns in their post-operative care. The goal of this study is to elucidate factors that confer risk of this outcome. Chart review was conducted for a consecutive series of immediate tissue expander reconstructions by the two senior authors. Data was collected for several preoperative and intraoperative variables, as well as the outcome of mastectomy flap necrosis. Of the 1566 breasts that were examined, 135 (8.6%) experienced flap necrosis. The cohorts with and without flap necrosis were well matched. Those with the outcome of interest had significantly higher rates of switching to an autologous method of reconstruction (31.9% vs 6.2%, p < 0.001). Regression analysis revealed smoking status, increased age, tumescent mastectomy technique, and …