The use of a filling block can improve the initial stability of the fixation plate in the open wedge high tibial osteotomy (OWHTO), and promote bone healing. However, the biomechanical effects of filling block structures and materials on OWHTO remain unclear. OWHTO anatomical filling block model was designed and built. The finite element analysis method was adopted to study the influence of six filling block structure designs and four different materials on the stress of the fixed plate, tibia, screw, and filling block, and the micro-displacement at the wedge gap of the OWHTO fixation system. After the filling block was introduced in the OWHTO, the maximum von Mises stress of the fixation plate was reduced by more than 30%, the maximum von Mises stress of the tibia decreased by more than 15%, and the lateral hinge decreased by 81%. When the filling block was designed to be filled in the posterior position of the wedge gap, the maximum von Mises stress of the fixation system was 97.8 MPa, which was smaller than other filling methods. The minimum micro-displacement of osteotomy space was –2.9 μm, which was larger than that of other filling methods. Compared with titanium alloy and tantalum metal materials, porous hydroxyapatite material could obtain larger micro-displacement in the osteotomy cavity, which is conducive to stimulating bone healing. The results demonstrate that OWHTO with a filling block can better balance the stress distribution of the fixation system, and a better fixation effect can be obtained by using a filling block filled in the posterior position. Porous HA used as the material of the filling block can obtain a better bone healing effect.