The ideal bone tissue engineering scaffold should have a precisely designed structure that provides complete interconnectivity of pores and maximum load bearing capacity. Inverted colloidal crystal (ICC) scaffolds have emerged recently as a highly organized three-dimensional (3D) environment for cell growth. ICC scaffolds possess a hexagonal close-packed geometry, which can be described as closely packed spherical pores arranged in a hexagonal crystal lattice. The ICC structure offers some obvious advantages for bone tissue engineering: (1) high degree of structural control, (2) invariably complete interconnectivity of pores, (3) 3D geometry resembling the morphology of trabecular bone and (4) the possibility of achieving high mechanical strength. Our laboratory introduces poly (DL-lactide-co-glycolide) (PLGA) ICC scaffolds for bone tissue engineering with highly controllable pore and inter-pore diameters. The average pore diameters and inter-pore diameters of scaffolds were controllable over a range of 100-330 μm and 50-175 μm, respectively. Additionally, the biocompatibility of these PLGA ICC scaffolds is demonstrated through in vitro cultures and in vivo implantation. From a fundamental point of view, the simplicity of its preparation and high degree of structural control provides excellent opportunities for understanding and manipulating cell cultures on the scaffold to produce ideal conditions for bone tissue engineering.