Our aim is to analyze the results of immediate breast reconstruction in women with macromastia after skin-reducing mastectomy (SRM), with an emphasis on complications and risk factors. Between 2008 and 2013, fifty women with hypertrophic breasts, aged 21-74 years, underwent immediate expander-based breast reconstruction after Wise pattern SRM. An inferiorly based de-epithelialized skin flap was sutured to the inferolateral border of the pectoralis major muscle and covered the expander. Thirty-five women had a unilateral and fifteen a bilateral procedure (total 65 breasts). In all cases, Becker-35 expanders of volume ranging from 365 to 685 cc were used. Risk factors (BMI, smoking, expander's size, preoperative irradiation, chemotherapy) and complications were recorded. Follow-up up to 60 months was compiled. In all cases, the myodermal pouch provided safe coverage and support of the expander. Postoperative complications occurred in 18 out of 65 breasts (27.6%) and included skin ischemia in 11 breasts (16.9%), late infection in two (3%), seroma and expander rotation in four and one, respectively (6.1 and 1.5%), and severe peri-prosthetical contraction in five breasts (7.6%). Statistical analysis showed that complications were significantly related to preoperative radiotherapy and smoking; no significant correlation was documented between complication rates and chemotherapy, BMI, age or expander's size. We suggest that the inverted-T SRM, creating a combined "myodermal" flap for the coverage of a Becker expander, is a useful single-stage reconstructive option for patients with macromastia. Preoperative radiotherapy is significantly related to higher postoperative complication rates, and may result in a less optimal reconstructive outcome. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.