BACKGROUND: Stem cell therapy is a promising new approach to wound healing. Stromal vascular fraction is a heterogeneous collection of cells, including adipose-derived stem cells, which are traditionally isolated using a manual collagenase-based technique. To our knowledge, this is the first human study that histologically assesses the potential of intraoperative intradermal injection of stromal vascular fraction on skin regeneration. METHODS: In this controlled study, 20 patients undergoing deep inferior epigastric perforator flap breast reconstruction and bilateral flank liposuction were included. Stromal vascular fraction was injected intradermally into one side of the abdominal suture line, while the other side served as a control. Outcome measures included analysis of stromal vascular fraction by flow cytometry, histological analysis of scar tissue, and scar photography. RESULTS: Cell yield for application and cell viability were 55.9 ± 28.5 × 106 and 75.1% ± 14.5%, respectively. Age and body mass index were positively correlated with the number of cells for application and adipose-derived stem cells. Mean vascular density, elastic fiber content, collagen maturity (scar index), epidermal thickness, and number of rete ridges all showed higher values on the treated side. Furthermore, the injected number of adipose-derived stem cells and pericytes positively correlated with vascular density. CONCLUSIONS: It is safe to speculate that intradermal stromal vascular fraction injection at the beginning of the healing process increases vascular density, collagen maturity and organization, elastic fiber content, epidermal thickness, epidermal-dermal anchoring of the scarring skin and is therefore responsible for improved skin regeneration. It is a viable and safe method that can be used as an adjunctive treatment in plastic surgery procedures where suboptimal wound healing is anticipated. LEVEL OF EVIDENCE IV: 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 .