Skin photoaging is a concern for many patients today, and it is important for dermatologists to evaluate new therapeutic approaches. This 6-month open-label study evaluated the effectiveness and safety of adapalene 0.3% gel in 40 Latin American women with signs of facial photoaging. Assessments at baseline, week 12, and week 24 included clinical severity grading, measurement of transepidermal water loss, hydration, and elasticity (Cutometer MPA 850®), evaluation of general skin tone and number of wrinkles (VISIA(®) Complexion Analysis System), and ultrasonography to measure changes in skin thickness. There were significant improvements in clinical grading of wrinkles (p < 0.01) with a reduction in mean severity score of 40% in forehead wrinkles, 52% in periorbital wrinkles, and 29% in perioral wrinkles. Melanin, transepidermal water loss, and hydration were improved, as were general skin tone and the number of wrinkles (p < 0.05). Measurement of skin thickness showed a non-significant improvement in the epidermis and dermis and a significant decrease of the elastosis band (11.6% at week 12 and 15.1% at week 24). Adapalene was well tolerated overall, although three patients discontinued the study due to skin irritation in the first month. We conclude that adapalene 0.3% gel is a new safe and effective approach to photoaging.