Introduction Breast cancer is the most frequently diagnosed tumor in women; globally, it accounts 23% of all cancer deaths. Breast reconstruction after oncologic surgery has become crucial to enhance patients’ quality of life and alleviate the psychological distress related to the disease. The aim of this study was to assess quality of life and esthetic satisfaction of breast cancer patients undergoing muscle-sparing skin-reducing breast reconstruction (MS-SR) with pre-pectoral implants. Methods Sixty-three patients who met definite oncological and reconstructive criteria were enrolled in the study. Specific questionnaires (EORTC QLQ-C30, QLQ-BR23) were administered preoperatively, 1, and 12 months after MS-SR breast reconstruction to evaluate patients’ QoL. Satisfaction with procedure and related Quality of Life were assessed through BREAST-Q questionnaire preoperatively and 12 months after surgery. Results Sixty-three breast cancer patients underwent MS-SR. Seventy-eight procedures were carried out; in 15 patients a bilateral reconstruction was performed. One month after surgery, both EORTC QLQ-C30 and QLQ-BR23 average scores demonstrated a slight drop since preoperative values, but a significant improvement in QoL was documented 12 months after BR (p