The aim of the present study was to evaluate bone formation after maxillary sinus augmentation using bovine bone substitute material Bio-Oss alone by means of clinical, histological, and histomorphometrical examination of human biopsies. Deproteinized bovine bone (DPBB, Bio-Oss) was used to fill cavities after elevation of the sinus mucosa following major sinus pneumatization. Twenty patients with edentulous posterior maxillae were treated with 20 sinus augmentation procedures using a 2-stage technique. Residual lateral maxillary bone height was less than 3 mm. Forty-nine Straumann endosseous implants were used to complete the implant-prosthetic rehabilitation. Forty cylinder-shaped bone biopsies were taken from the augmented maxillary region 8 months after grafting during the second-stage surgery before implant placement. All implants were loaded 3 months after insertion, and no failures were recorded. Histomorphometrical analysis showed an average percentage of newly formed bone of 17.6% (± 2.8%) and a proportion of residual bone substitute material of 29.9% (± 4.9%) of the total biopsy area. Intimate contact between newly formed bone and Bio-Oss was detected along 28.2% (± 6.8%) of the particle surfaces. The results also showed that in all cases, the DPBB granules had been interconnected by bridges of vital newly formed bone. Inorganic bovine bone appears to be biocompatible and osteoconductive, and it can be used with success as a bone substitute in maxillary sinus augmentation procedures.