Background: Millisecond-pulsed Nd:YAG lasers have been developed for the treatment of reticular leg veins. Objective: We evaluated the effectiveness of a single treatment with a 50 millisecond 1064 nm Nd:YAG laser in the treatment of reticular veins of the lower extremity. Methods: Twenty patients with reticular veins measuring 1.0 to 3.0 mm in diameter received one treatment with a 1064 nm Nd:YAG laser (Coolglide, Altus, Burlingame, Calif) at fluences of 100 J/cm² and 50 millisecond pulse duration. Symmetric matched areas that were left untreated served as the control. Eleven patients were pretreated with a topical anesthetic cream for 1 hour before treatment and wore compression stockings for 5 days after treatment. Nine patients were treated without topical anesthesia and did not wear compression stockings. Percent clearing and side effects were determined by 3 nontreating physicians (at each respective site) comparing projected Kodachrome images 1 month and 3 months after treatment. Patients also performed a self-assessment of their results. Results: Two-thirds of vessels measuring 1 to 3 mm in diameter cleared more than 75% with one treatment. Larger vessels appeared to improve more than smaller vessels. Immediate treatment discomfort was tolerable. Side effects were minimal and included superficial thrombosis, delayed bruising, hyperpigmentation, and matting. Conclusion: Millisecond-pulsed Nd:YAG lasers used with 50 millisecond pulses are effective in the treatment of reticular leg veins. (J Am Acad Dermatol 2003;48:76-81.)