Background: Asia is located around equator with all year sun exposure. That is why Asians are more susceptible to aging caused by ultraviolet, or called as photoaging. Dyspigmentation and wrinkle is the most visible clinical sign of skin photoaging, making them the main target to treat.Objective: To investigate the efficacy of fractional Carbon Dioxide (CO2) laser-Assisted amniotic membrane stem cell conditioned medium (AMSC-CM) plus vitamin C in Asian skin photoaging.Patients and methods: This were a randomized comparative clinical study in photoaged patients. Experimental group received amniotic membrane stem cell conditioned medium (AMSC-CM) plus vitamin C mixture after fractional CO2 laser, while another group received AMSC-CM after fractional CO2 laser. The formulation was applied three times with 4 weeks interval. Fractional CO2 laser was used to assist epidermal penetration. Wrinkle, pore, spot, and skin tone were evaluated before treatment and 4 weeks after last session.Results: This study included 60 women with an average age of over 50 years. Wrinkle and pore improvement after therapy on AMSC-CM plus Vitamin C mixture group were significantly better than group who only received AMSC-CM (p value < 0.05). No serious adverse effect was observed during the study.Conclusion: AMSC-CM plus Vitamin C mixture application after laser fractional CO2 is promising as rejuvenation treatment in Asian skin.