The use of autologous fat grafting is ideal in breast reconstruction. However, published data on long-term outcomes and instrumental results of fat grafting to the breast are lacking. The purpose of this study was to review the authors' experience of fat grafting, evaluating the effects related to the use of enhanced stromal vascular fraction (e-SVF) and fat grafting with platelet-rich plasma (PRP) in the maintenance of fat volume in breast reconstruction, comparing the results with a control group. Twenty-three patients aged 19-60 years affected by breast soft tissue defects were analyzed at the Plastic and Reconstructive Department of the University of Rome Tor Vergata. Ten patients were treated with SVF-enhanced autologous fat grafts, and 13 patients were treated with fat grafting + platelet-rich plasma. The patients in the control group (n = 10) were treated with centrifuged fat grafting injection according to Coleman's procedure. The patients treated with SVF-enhanced autologous fat grafts showed a 63% maintenance of the contour restoring and of three-dimensional volume after 1 year compared with the patients of the control group treated with centrifuged fat graft, who showed a 39% maintenance. In those patients who were treated with fat grafting and PRP, we observed a 69% maintenance of contour restoring and of three-dimensional volume after 1 year. As reported, the use of either e-SVF or PRP mixed with fat grafting produced an improvement in maintenance of breast volume in patients affected by breast soft tissue defect.