BACKGROUND: Numerous methodologies and algorithms have been suggested to enhance fat graft survival, including the usage of stromal vascular fraction (SVF) and platelet-rich plasma (PRP), but no long-term studies are available. OBJECTIVES: This single-center prospective, case-controlled study investigated the safety and efficacy of combining a modified Baker-designed lateral SMASectomy or plication face lift with simultaneous anterior mid-face grafting into site-specific compartments by (1) conventional Coleman's technique or (2) Yoshimura's cell-assisted lipografting technique. METHODS: On the voluntary principle, candidates selected one of four techniques for volumization of their mid-face: conventional fat grafting; PRP-assisted fat grafting; SVF-assisted fat grafting; and PRP/SVF- assisted fat grafting. For comparison data, comparable fat volumes, SVF volumes and nucleated cells, and PRP volumes and platelet concentrations were injected into each designated group. Indirect volume retentions were determined by standardized Vectra 3D analyses up to 1 year. RESULTS: PRP, SVF, and PRP/SVF cell supplementation of processed fat resulted in statistically significant percent mean graft retention over their baseline control at 12 months (p < 0.01). The use of either PRP or SVF alone resulted in almost equal outcomes. Combining cell populations provided no additional advantage over single cellular therapy. Complications were negligible. CONCLUSIONS: Autologous fat grafting continues to be a viable adjunct in facial aesthetic surgery. With refinements in the entire grafting process and the potential benefits of autologous cell approaches with SVF and PRP, future evidence-based controlled studies under regulatory approval may improve graft survival in a safe and effective manner. LEVEL OF EVIDENCE III: 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.