This study aimed to evaluate the impact of three types of block bone substitute material on bone formation and graft resorption in vivo. Standardized bone defects (n = 4 defects/animal) were created in the calvaria of nine dogs. Block bone substitutes made of deproteinized bovine bone mineral (DBBM), beta-tricalcium phosphate (β-TCP) and a mixture alpha-TCP and hydroxyapatite (α-TCP/HA) were inserted into the bone defects. A fourth defect was left untreated (empty). All sites were covered with a collagenous membrane. Block biopsies were harvested at 3, 6 and 12 months post-implantation and analyzed by micro-CT and histology. Biomaterial absorption was minimal and incorporation within the defect margin was good for all biomaterials. However, β-TCP demonstrated a relatively greater volume of new bone formation and less residual material volume when compared with DBBM and α-TCP/HA. Conversely, α-TCP/HA showed higher osteoconductive potential and a greater new bone area compared with the other two biomaterials. The block bone substitutes used in the present in vivo study showed advantageous in terms of maintenance of their original form in bony defect. However, the positive impact of all biomaterials on new bone formation and replacement of bone was minor even at 12 months. These findings indicate that block bone substitutes are not well suited to vertical bone augmentation. Further investigations are required to improve the insufficient new bone volume for promising clinical results.