Bovine origin matrix has been widely used in clinical applications and investigated by various research institutions. However, the potential factors that influence bone regeneration are still not thoroughly understood and need further investigations. In this study, bone regeneration properties of anorganic bovine bone matrix (ABBM), organic-containing bovine bone matrix (OBBM), and widely acknowledged anorganic bovine bone matrix (Bio-Oss) were compared. Besides, the correlations between physiochemical characterizations and bone regeneration properties of the three xenografts were also investigated. Physiochemical characterizations were measured by special instrumentations. In animal studies, the three xenografts were implanted into 8-mm-diameter cranial defects of 16 New Zealand white rabbits. The biological effects were evaluated by micro-computed tomography and histomorphometric analysis after 6 and 12 weeks of implantation. The physical characterizations showed that anorganic bovine bone matrix and Bio-Oss had more nanostructures, larger surface area, bigger pore volume, and bigger pore size than that of organic-containing bovine bone matrix. The chemical characterizations showed that anorganic bovine bone matrix and Bio-Oss had higher crystallinity than that of organic-containing bovine bone matrix, and organic-containing bovine bone matrix contained organic nitrogen (N) component. In vivo, anorganic bovine bone matrix and Bio-Oss possessed better bone regeneration properties than that of organic-containing bovine bone matrix. Taken together, nanostructures, larger surface area, bigger pore volume, and bigger pore size of xenografts played an active role in new bone formation. Besides, lower crystallinity and organic N element of xenografts produced a positive effect on graft degradation. The abovementioned findings could provide theoretical basis for better choice in clinical applications and better manufacturing hydroxyapatitederived bone graft in the future.