Background and Objective: Patient-reported outcomes and blinded observer rating scales are subjective and unreliable but are extensively utilized to evaluate cosmetic office-based treatments, including ablative lasers. This study aims to assess the practicality of using noninvasive and minimally invasive methods for objective skin assessment following a skin rejuvenation treatment. Study Design/Materials and Methods: Twelve patients received a single 1,470/2,940 nm laser treatment for facial rejuvenation. Assessments were performed before treatment, and 7 days, 3 weeks, and 3 months posttreatment. Images were taken with the VISIA Skin Analysis System to measure wrinkles, textures, pores, ultraviolet (UV) spots, brown spots, red areas, and porphyrins. Other non-invasive skin measurements-highresolution ultrasonography, optical coherence tomography, transepidermal water loss and BTC 2000-were used to measure epidermal/dermal thickness, blood flow, surface roughness, wrinkle depth, attenuation coefficient, elasticity, laxity, and viscoelasticity. Microbiopsies (0.33 mm in diameter or the equivalent of a 23-gauge needle) were collected for histology and gene expression of tissue rejuvenation. Results: Significant improvement in facial skin aesthetics after laser treatment was recorded in UV spots, brown spots and pores after 3 weeks and in UV spots and brown spots after 3 months. The dermal attenuation coefficient decreased significantly at 3 weeks, while blood flow 0.5 to 0.7 mm below the skin surface increased significantly between 5 days and 3 weeks following treatment. Epidermal hyaluronic acid expression assessed by immunostaining and expression of inflammatory genes were elevated at 7 days posttreatment compared with untreated or 3 months posttreatment. There were no statistically significant changes in collagen or elastin-related genes between groups at the studied parameters. Conclusion: Non-invasive devices can be effectively used to provide objective measurements of skin structure, pigmentation, blood flow, and elasticity to assess the efficacy of facial skin rejuvenation treatments. Furthermore, microbiopsies can objectively evaluate facial skin rejuvenation without scarring. Using non-invasive skin imaging, a single treatment with the 1,470/2,940 nm laser was observed to be effective in improving skin appearance after 3 months, namely in reducing UV spots and brown spots, without significant changes in the tissue at the molecular level, as assessed by microbiopsy. Lasers Surg.