Abstract Background The use of stem cells derived growth factors is representing a novel treatment modality in facial rejuvenation. Nowadays, skin needling is considered a very famous treatment of skin aging. However, the addition of such derived products, augments its therapeutic efficacy in the management and delay of skin aging. Objective Comparing the effect of amniotic fluid mesenchymal stem cell derived conditioned media (AF‐MSC‐CM) combined with skin needling versus the needling alone in the management of facial aging. Methods Both sides of the face of ten volunteers, suffering from facial aging, were treated with five sessions of skin needling, 2 weeks apart. After skin microneedling, AF‐MSC‐CM was added topically to the right side only. Clinical, histological, and morphometrical assessment of the treated skin was done at 1 month after the last session. Results The percentage of improvement of aged skin increased significantly on the combined treated side (AF‐MSC‐CM and dermaroller [DR]), when compared with the other side (DR only) ( P < .001). Remodeling of the dermal structures was observed mainly on the combined side. Meanwhile, histometry of the epidermis revealed a significant increase in the epidermal thickness on both treated sides. Conclusion AF‐MSC‐CM combined with skin needling was more efficient in managing facial aging than skin needling alone.