The appearance of facial expression wrinkles is the result of chronic contraction of mimic muscles. Nifedipine is a dihydropyridinic calcium antagonist which blocks muscular cells' calcium channels, therefore inhibiting their contraction. We assumed that topical nifedipine was able to relax mimic muscular fibres in the same way, thus reducing the depth of wrinkles. We performed a clinical and experimental study, enrolling 64 female patients with periocular wrinkles. They applied a cream containing 0.5% nifedipine (Antrox; Bracco, Milan, Italy) once daily for 90 days. The length and depth of wrinkles (measured by a digital profilometer), moisturizing of periocular skin (measured by a corneometer), and trans-epidermal water loss (TEWL; measured by a tewameter), were evaluated. All parameters were measured before the beginning of treatment, and 45 and 90 days later. At the end of the study, topical nifedipine proved statistically effective in reducing the depth of wrinkles. No significant differences in the length of wrinkles were recorded. No significant changes were observed in moisturizing. TEWL gradually improved, although without statistical significance. On the basis of the results of this study, 0.5% nifedipine cream seems to be effective in reducing the depth of periocular wrinkles. Other studies are necessary in order to confirm these results.