Objectives: There exist only few human histomorphological studies on the long- term behavior of bone substitute materials after sinus lift. This study shows a systematic histomorphometric analysis of two human bone biopsies 1 and 5 years after grafting with a xenogenic bovine bone substitute material (BSM). Methods: 2 healthy patients received grafting of the maxillary sinus with a xenogenic BSM (Bio-Oss). Due to personal circumstances, implant placements could not performed before 10.5 months or even 4 years 7.5 months after the augmentation procedures. During preparation of the implant site, trephine bur bone biopsies were harvested. After fixation and dehydration through an ethanol gradient and defatting in xylene, the obtained trephine biopsies were embedded without decalcification in methacrylate. The untreated blocks underwent microcomputed tomography (µ-CT). 3-D reconstructions provided visualization of the complex bone-biomaterial interactions. The volume ratios of the following compartments were determined: non-mineralized soft tissue, newly formed (mineralized) bone and (persistent) bone substitute material. Afterwards, sec- tions of a thickness of approximately 80µm were made and conventionally HE-stained. A descriptive analysis of the bony healing was performed. Results: For both investigated specimen, µ-CT revealed formation of bone tissue with good and tight bony incorporation of the BSM. For the specimen obtained after 10.5 months, 30% of new-formed bone with 26.6% of remaining BSM was calculated. After 4 years and 7.5 months, 32.8% of new bone with 15.8% residual BSM was seen. In the histological examination, between the Bio-Oss particles, a directed, well vascularized bony tissue with close contact to the individual BSM particles was seen. For both time points, only superficial resorptions could be detected. An osteoconduction into small porous structures with establishment of osteons was observed. However, the bony tissue surrounding the BSM particles showed considerable differences for the two investigated time points. While after 10.5 months an active bone regeneration with all signs of desmal ossification could be observed, after 55.5 months a de facto completed ossification with uniformly directed lamellar bone was detected. Conclusions: In these two rare cases of human long-term biopsies of a xenogenic BSM a completed bony integration without extensive resorption of the BSM particles could be detected with differences between the two time points (immature vs. mature bone). Altogether, a good integration in the surrounding bone with good osteoconduction and a high biocompatibility was seen. Keywords: sinuslift, xenogenic bone substitute, histomorphometry