Tetrabone is a newly developed granular artificial bone. The 1-mm Tetrabone has a four-legged structure. In this study, the long-term effect of implanting Tetrabone or β-TCP granules in rabbit femoral cylindrical defects was evaluated. The rabbits were euthanized at 4, 13, and 26 weeks after implantation. Micro-CT was conducted to evaluate the residual material volume and the non-osseous tissue volume. New bone tissue areas were measured by histological analysis. Micro-CT imaging showed that the residual material volume in the β-TCP group had decreased significantly at 4 weeks after implantation (P < 0.05) and that the β-TCP granules had nearly disappeared at 26 weeks after implantation. In the Tetrabone group, it did not significantly change until 13 weeks after implantation; it then continued to decrease slightly until 26 weeks after implantation. The non-osseous volume increased in the β-TCP group, whereas that of the Tetrabone group decreased (P < 0.05). Histological examination showed that the new bone areas were significantly greater in the Tetrabone group than in the β-TCP group at 13 and 26 weeks. In conclusion, resorption of β-TCP granules occurs before sufficient bone formation, thereby allowing non-osseous tissue invasion. Tetrabone resorption progressed slowly while the new bone tissues were formed, thus allowing better healing. Tetrabone showed better osteoconductivity, whereas the β-TCP granules lost their function over a long duration. These results may be caused by the differences in the absorption rate of the granules, intergranular pore structure, and crystallinity of each granule.