The biomechanical influence of thoraco-lumbo-sacral bracing, a commonly employed treatment in scoliosis, is still not fully understood. The aim of this study was to compare the immediate corrections generated by different virtual braces using a patient-specific finite element model (FEM) and to analyze the most influential design factors. The 3D geometry of three patients presenting different types of curves was acquired with a multi-view X-ray technique and surface topography. A personalized FEM of the patients' trunk and a parametric model of a virtual custom-fit brace were then created. The installation of the braces on the patients was simulated. The influence of 15 design factors on the 3D correction generated by the brace was evaluated following a design of experiments simulation protocol allowing computing the main and two-way interaction effects of the design factors. A total of 12,288 different braces were tested. Results showed a great variability of the braces effectiveness. Of the 15 design factors investigated, according to the 2 modalities chosen for each one, the 5 most influential design factors were the position of the brace opening (posterior vs. anterior), the strap tension, the trochanter extension side, the lordosis design and the rigid shell shape. The position of the brace opening modified the correction mechanism. The trochanter extension position influenced the efficiency of the thoracic and lumbar pads by modifying their lever arm. Increasing the strap tension improved corrections of coronal curves. The lordosis design had an influence in the sagittal plane but not in the coronal plane. This study could help to better understand the brace biomechanics and to rationalize and optimize their design.