The clinical use of platelet-rich plasma (PRP) for a wide variety of application has been reportedly employed most prevalently in problematic wounds, maxillofacial and hemi-facial atrophy, Romberg Syndrome, and diabetic foot ulcers. To our knowledge, PRP has never been described in the enhancement of fat grafting during tissue-engineering application in vivo. The authors describe the preparation of PRP and its use in a series of 43 patients who underwent plastic, reconstructive, and maxillofacial surgery for chronic lower extremity ulcers (n = 18) and multiple facial applications (n = 25). PRP mixed with fat grafting was used in 76% patients affected by multiple facial diseases and in 88.9% patients affected by lower extremity ulcers. PRP injection alone was used in the remaining patients. The authors observed that after a 7.1-week and 9.7-week (average) course of twice-daily wound treatment with PRP suspended on a collagen base, 61.1% and 88.9% of chronic lower extremity ulcers underwent to 100% reepithelization compared with 40% and 60% of controls (n = 10) treated with hyaluronic acid and collagen medication. In patients treated with reconstructing three-dimensional projection of face by fat grafting and PRP, we observed a 70% maintenance of contour restoring and three-dimensional volume after 1 year compared to only 31% of controls (n = 10) treated with fat grafting alone. In vitro, PRP induced a significant increase in the number of adipose-tissue-derived stem cells compared to control cultures. These results documented that PRP accelerates chronic skin ulcer reepithelization and improves maintenance and function of fat graft in patients who underwent plastic reconstructive surgery, possibly by stimulating adipose-tissue-derived stem cell proliferation.