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The purpose of this study was to evaluate the repair process in rat calvaria filled with synthetic biphasic bioceramics (Plenum^® Osshp-70:30, HA:βTCP) or autogenous bone, covered with a polydioxanone membrane (PDO). A total of 48 rats were divided into two groups (<i>n</i> = 24): particulate autogenous bone + Plenum^® Guide (AUTOPT+PG) or Plenum^® Osshp + Plenum^® Guide (PO+PG). A defect was created in the calvaria, filled with the grafts, and covered with a PDO membrane, and euthanasia took place at 7, 30, and 60 days. Micro-CT showed no statistical difference between the groups, but there was an increase in bone volume (56.26%), the number of trabeculae (2.76 mm), and intersection surface (26.76 mm²) and a decrease in total porosity (43.79%) in the PO+PG group, as well as higher values for the daily mineral apposition rate (7.16 µm/day). Histometric analysis presented material replacement and increased bone formation at 30 days compared to 7 days in both groups. Immunostaining showed a similar pattern between the groups, with an increase in proteins related to bone remodeling and formation. In conclusion, Plenum^® Osshp + Plenum^® Guide showed similar and sometimes superior results when compared to autogenous bone, making it a competent option as a bone substitute.