Background: Our objective was to conduct a comprehensive analysis of the reproducibility of foot and ankle anthropometric measurements with a three-dimensional (3D) optical scanner. Methods: We evaluated thirty-nine different anthropometric parameters obtained with a 3D Laser UPOD-S Full-Foot Scanner in a healthy population of twenty subjects. We determined the variance of the measurements for each foot/ankle, and the average variance among different subjects. Results: For 40 feet and ankles (15 women and 5 men; mean age 35.62 +/− 9.54 years, range 9–75 years), the average variance was 1.4 ± 2 (range 0.1 to 8). Overall, the mean absolute measurement error was <1 mm, with a maximum variance percentage of 8.3%. Forefoot and midfoot circumferences had a low variance <2.5, with variance percentages <1%. Hindfoot circumferences, malleolar heights, and the length of the first and fifth metatarsal to the ground contact points showed the highest variance (range 1 to 7). Conclusions: The UPOD-S Full-Foot optical Scanner achieved a good reproducibility in a large set of foot and ankle anthropometric measurements. It is a valuable tool for clinical and research purposes.