|Background: Previously, the reverse electrodialysis (RED) system was found to improve transdermal drug delivery compared to passive diffusion. Objectives: To evaluate antiaging effect and safety profile of iontophoresis mask patch using RED technique. Methods: This study was a prospective, spilt-face, controlled trial comparing iontophoresis mask patch using RED technique with passive diffusion mask patch. Clinical studies were performed on 20 Korean women for 5 weeks. We applied iontophoresis mask patch using RED on the right side of the face and passive diffusion mask patch on the left side of the face and treated four times at weekly intervals. Both mask patches contain same materials (SYN-AKE, oligo hyaluronic acid, leuphasyl, argireline etc.). Clinical effect was assessed by measuring erythema index, melasma index, stratum corneum hydration, and skin roughness at baseline, week1 (after 1 treatment), week 4 (after 4 treatment), and week 5 (1 week after 4 treatment). Results: After 4 treatment, improvements in the erythema index, stratum corneum hydration and skin roughness were significantly greater in the test side than in the control side. However, there was no statistically significant improvement in the melsma index on both side. Conclusion: This study suggests that iontophoresis mask patch using RED has a greater effect on antiaging than passive mask patch.