Topical tretinoin formulation is still unavailable in Japan. Because topical retinol, which is less potent but may cause less irritation, is available here, we have performed a randomized, blinded, vehicle-controlled study on the face using a once-nightly regimen for the treatment of mild photoaging in middle-aged Japanese females. First, a 26-week study was conducted in 57 subjects with a 0.075% retinol cream and its vehicle on each half side of the face. Three of the 57 subjects withdrew from the study due to irritation, although this rate was much smaller than that noted in our previous study with topical tretinoin. After 26 weeks, the rates of photoaging improvement were significantly higher on the retinol side: 27 out of 54 (50%) versus 13 (24%) for the fine wrinkling and 15 out of 54 (28%) versus 1 (2%) for deep wrinkling. A similar trial with a 0.04% retinol cream for 13 weeks revealed less prominent improvements in fine wrinkling but minimal irritation. From these data, we think that retinol creams, especially 0.04% cream, are suitable for daily use in the general population because of the low irritancy, even for those with sensitive skin.