Clinical assessment of immediate in-brace effect of braces designed using CAD/CAM and FEM vs. only CAD/CAM for conservative treatment of AIS, using a randomized blinded and controlled study design. Forty AIS patients were prospectively recruited and randomized into two groups. For 19 patients (control group), the brace was designed using a scan of patient's torso and a conventional CAD/CAM approach (CtrlBrace). For the 21 other patients (test group), the brace was additionally designed using finite element modeling (FEM) and 3D reconstructions of spine, rib cage and pelvis (NewBrace). The NewBrace design was simulated and iteratively optimized to maximize the correction and minimize the contact surface and material. Both groups had comparable age, sex, weight, height, curve type and severity. Scoliosis Research Society standardized criteria for bracing were followed. Average Cobb angle prior to bracing was 27A degrees and 28A degrees for main thoracic (MT) and lumbar (L) curves, respectively, for the control group, while it was 33A degrees and 28A degrees for the test group. CtrlBraces reduced MT and L curves by 8A degrees (29 %) and 10A degrees (40 %), respectively, compared to 14A degrees (43 %) and 13A degrees (46 %) for NewBraces, which were simulated with a difference inferior to 5A degrees. NewBraces were 50 % thinner and had 20 % less covering surface than CtrlBraces. Braces designed with CAD/CAM and 3D FEM simulation were more efficient and lighter than standard CAD/CAM TLSO's at first immediate in-brace evaluation. These results suggest that long-term effect of bracing in AIS may be improved using this new platform for brace fabrication. NCT02285621.