Botulinum-A exotoxin (BTX-A) can be used cosmetically to improve rhytides, particularly of the upper one-third of the face. In this study, fifteen women had BTX-A (BOTOX, Allergan, Inc.) injected into the orbicularis oculi muscle. One lower eyelid received two units just subdermally in the midpupillary line three millimeters below the ciliary margin. The opposite periocular area received two units BTX-A in the lower eyelid with 12 units BTX-A injected into the lateral orbital (“crow's foot”) area. Three injections of four units each were placed 1.5 cm from the lateral canthus, each 1 cm apart. Patients and physicians independently evaluated the degree of improvement (grade 0 = no improvement, grade 1 = mild improvement, grade 2 = moderate improvement, and grade 3 = dramatic improvement). An independent photographic analysis was performed. Patients reported a grade of 0.73 when two units were injected alone into the lower lid, and a grade of 1.9 when the lower eyelid and the lateral orbital areas were injected. Physician assessment was grade 0.7 with injection of the eyelid alone and grade 1.8 with injection of the lower eyelid and lateral orbital area. Single investigator photographic analysis demonstrated that 40% of the subjects who had injection of the lower eyelid alone had an increased palpebral aperture (IPA), while 86% of the subjects who had injection of the lower eyelid and lateral orbital area had an IPA. Subjects receiving two units alone had an average 0.5 mm IPA and a mean 1.3 mm IPA at full smile. Concomitant treatment of the lateral orbital area produced a mean 1.8 mm IPA at rest and a mean 2.9 mm IPA at full smile. The results were more notable in the Asian eye. Two units of BTX-A injected into the lower eyelid orbicularis oculi muscle improves infraorbital wrinkles, particularly when used in combination with BTX-A treatment of the lateral orbital area.