Background: The reconstruction of large breasts carries a heightened risk profile. While skin-reducing mastectomy (SRM) techniques facilitate the correction of breast ptosis, they are frequently associated with a high incidence of vascular complications. This study compares two SRM techniques—the horizontal incision and the classic inverted T incision—by examining their clinical and surgical outcomes. Methods: We retrospectively analyzed data from 24 patients (30 breasts) who underwent SRM with immediate prosthetic reconstruction between 2019 and 2023 at the European Institute of Oncology in Milan, Italy. Our comparison focused on breast aesthetic outcome, reconstruction quality, complication rates (early and late), and patient satisfaction, utilizing the BREAST-Q questionnaire to gauge the latter. Results: Among the 24 patients included in the study, 16 (20 breasts) were treated with the inverted T technique, and 8 (10 breasts) with the horizontal incision approach. A higher overall complication rate was observed with the inverted T technique compared to the horizontal method, with early complications outnumbering late ones. The most common issues were recurrent seroma and skin necrosis leading to implant exposure. Notably, there were no cases of implant infection. Although the horizontal incision technique achieved slightly higher patient satisfaction scores, the difference was not statistically significant. Discussion: The inverted T and horizontal incision techniques each have unique benefits and drawbacks. Our findings indicate enhanced patient satisfaction and reduced complication rates with the horizontal incision technique. The selection of the technique should be customized based on the patient’s individual risk factors, tissue quality, and preferences.