Background: Aging is a multifactorial process that involves all components of the skin. Both intrinsic and extrinsic forces play a role in this aging process. A new patented protein mix derived from red deer umbilical cord lining stem cell conditioned media (Calecim® Multi Action Cream, CellResearch Corporation, Singapore) has been developed to improve the signs of aging. The extract is the conditioned media from umbilical cord lining mesenchymal stem cell culture in basal media and consists of a mixture, in specific proportions, of cytokines, growth factors, extracellular matrix proteins, amino acids, peptides, and other proteins. It has been developed to increase epidermal cell turnover and stimulate fibroblast function, reducing the appearance of pigmentation, fine lines, and redness, and to restore skin elasticity. Objective: The objective of this IRB-approved, prospective, randomized, double-blind, split-face, placebo-controlled clinical trial was to compare the efficacy of red deer mesenchymal stem cell extract (RCE) versus vehicle for facial rejuvenation. Methods: The trial involved 40 healthy subjects with moderate to severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical RCE cream and vehicle cream to the other half of the face. Treatment was continued for 3 months, and evaluations were performed in a double-blind fashion. Results: Both sides of the face achieved significant improvement. Blinded investigator assessments did not detect any statistically significant differences between the two halves of the face in terms of efficacy, safety, or tolerability. Subject evaluations demonstrated superiority of the active treatment side. Conclusion: Red deer umbilical cord lining mesenchymal stem cell extract was effective in rejuvenating the aging face as demonstrated by investigator and subject measures. J Drugs Dermatol. 2019;18(4):363-366.