In this case series, a systematic histomorphometric analysis of two human bone biopsy specimens was conducted 1 and 5 years after grafting with a xenogeneic bovine bone substitute material (BSM). While the 1-year specimen still showed extensive signs of an active desmal ossification, the specimen after 5 years mainly showed mature lamellar bone without bone turnover or remodeling. A completed bony integration without extensive resorption of the BSM particles could be detected. Altogether, a good integration in the bone with osteoconduction and a high biocompatibility was seen.