Background <p>Autologous fat grafting is widely used in reconstructive and aesthetic surgery, yet long-term volume retention and postoperative complications remain unpredictable. Numerous fat processing techniques have been developed to optimize graft survival. However, clinical practice remains heterogeneous, and consensus regarding an optimal processing method is lacking. This systematic review evaluates comparative clinical outcomes associated with different fat-processing techniques used in autologous fat grafting.</p> Methods <p>A systematic review was conducted according to PRISMA guidelines. PubMed, MEDLINE, and Embase were searched from inception to November 2025 for comparative human clinical studies evaluating two or more fat-processing techniques. Processing methods were categorized as centrifugation, decantation, passive filtration, or active wash–filtration. Randomized controlled trials were assessed using ROB 2, and non-randomized studies using ROBINS-I. </p> Results <p>Fifteen comparative clinical studies met the inclusion criteria. No single fat-processing technique consistently outperformed all others across reported outcomes. Across heterogeneous study designs and indications, active wash–filtration techniques were more commonly associated with lower reported rates of fat necrosis and cyst formation, greater volume retention, and higher processing efficiency compared with centrifugation, decantation, and passive filtration; however, these findings were inconsistent and derived primarily from non-randomized evidence. Centrifugation demonstrated variable performance, with higher complication rates reported in some breast applications but acceptable or favorable outcomes in selected aesthetic indications. Passive filtration and low-pressure decantation yielded acceptable results in specific clinical contexts.</p> Conclusions <p>Current evidence does not support a universally superior fat-processing technique. While active wash–filtration techniques have been associated with favorable trends in volume retention, complication profiles, and operative efficiency in some studies, these observations should be interpreted cautiously given substantial heterogeneity in study design, indications, and technical reporting. Selection of fat-processing technique should therefore be individualized based on anatomical site, graft volume, and operative workflow. Well-designed, standardized, adequately powered prospective studies are needed to clarify the comparative clinical impact of fat-processing methods.</p> <p>Level of Evidence: Not gradable</p>