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Fat grafting has been used extensively in plastic surgery in the past two decades. Here, the authors report the retrospective comparison of patients who underwent fractionated fat injection to blend the lid-cheek junction with those who had regular fat injection.After obtaining institutional review board approval, a retrospective review of patients who underwent lower blepharoplasty with fractionated fat injection for blending the lid-cheek junction from January of 2014 through October of 2015 was performed. The results were compared to those of lower blepharoplasty patients who did not have fractionated fat injected before January of 2014. Twelve prospectively selected patients underwent histopathologic and gene expression comparisons.A comparison of complications between the two groups revealed no significant differences. Furthermore, there was no significant difference between the two groups for sequelae of fractionated fat injection and regular fat injection. The gene expression analysis of the fractionated and regular fat did not show any difference between undifferentiated and differentiated cells. In addition, Oil Red O staining of the fractionated and regular fat after differentiation showed that cells from both fat groups differentiated equally well.Fractionated fat injection appears to be a safe addition in blending the lid-cheek junction in the five-step lower blepharoplasty. There is no fat nodule formation with injection of fractionated fat injection compared with injection of regular fat performed superficially in the tear trough area. Contrary to what has previously been shown, the presence of viable cells in fractionated fat was noted.Therapeutic, III.