The damaging effects of UVA radiation have been well-documented. UVA radiation is known to induce molecular, cellular, and clinical damage. Such harm may lead to photoaging, immune system depression, altered gene expression, or oncogene and tumor suppressor gene modulation, all of which are partly responsible for the development of skin cancer. In parallel to an increased understanding of the added damage caused by UVA radiation, progress has been made in sunscreen formulation. A variety of UVA filters are now available for formulators to combine with UVB filters to reach high-level photostable protection using a minimum concentration of active ingredients. The efficacy of products that contain these UV filter combinations usually is determined by noninvasive assessments, which cause either UVA-induced erythema or skin pigmentation. However, the biologic relevance of these end points for UVA radiation-induced skin damage is unknown. In our study, we confirm that the assessment of UVA radiation-induced gene expression in skin specimens obtained from UVA-irradiated human skin by quantitative real-time polymerase chain reaction is a sensitive, reliable, and robust method to prove the efficacy of 2 daily moisturizers containing broad-spectrum sunscreen. Specifically, we demonstrate in vivo that topical application of a daily moisturizer with broad-spectrum sunscreen prevents UVA radiation-induced transcriptional expression of genes that are directly linked to skin aging (ie, matrix metalloproteinase 1 [MMP-1]) and also reflect the skin's antioxidative stress defense response (ie, catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx]). Furthermore, we demonstrate that the protection against UV-induced skin damage provided by products with different sun protection factor (SPF) but the same UVA protection factor (UVA-PF) is similar, which emphasizes the importance of high UVA protection to maintain unaltered essential biologic functions. These data indicate that the use of a daily moisturizer containing broad-spectrum sunscreen with a well-balanced SPF/UVA-PF ratio on a regular basis is beneficial for human skin.