Background: Leg veins can be effectively treated with lasers. However, the optimal pulse duration for small leg veins has not been established in human studies with a Nd:YAG laser. Objectives: The purpose of this study was to investigate a range of pulse durations to determine an optimal pulse duration for clearance of leg veins. Study Design/Materials and Methods: After mapping and photo documentation of the leg veins to be treated, a variable pulse duration Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser (3-100 milliseconds) was used in a single test site session. Pulse durations of 3, 20, 40, 60, 80, and 100 milliseconds were used. At the 3-week follow-up, the optimal pulse duration was defined as that pulse duration which resulted in the most complete clearance of vessels with the least side effects. Up to 20 vessels were then treated using the established ''optimal'' pulse duration. Final evaluation was at 16 weeks after the initial visit. Three blinded observers rated the percent of vessels completely cleared based on initial and final photographs. Results: Eighteen patients completed the study. Fluence thresholds for immediate vessel changes varied depending on spot size and vessel diameter, with larger fluences required for smaller spot sizes and smaller vessels. Shorter pulse durations ( 20 milliseconds) were associated with occasional spot sized purpura and spot sized post-inflammatory hyperpigmentation. Longer pulse durations (40-60 milliseconds) achieved superior vessel elimination with less post-inflammatory hyperpigmentation. With a single laser treatment, 71% of the treated vessels cleared. Conclusions: Compared to shorter pulses (<20 milliseconds), longer pulses may provide gentler heating of thevessel and a greater ratio of contraction to thrombosis.