Purpose: Lack of bone height in the posterior maxilla often necessitates augmentation prior to or simultaneously with dental implant placement. The purpose of this clinical study was to evaluate the use of the natural bone mineral Bio-Oss alone or in combination with autogenous bone in sinus floor elevations performed as 1- or 2-step procedures. Materials and Methods: Thirty-eight patients required sinus augmentation. Natural bone mineral alone was used in sinus floor augmentation in 21 patients. In 13 patients, a mixture of the bone substitute and autogenous bone was used, and in 4 patients autogenous bone alone was used. In all of the patients, samples were taken for biopsy 3 to 8 months postoperatively, and bone regeneration was evaluated histologically and histomorphometrically. Results: In all patients, the amount of new bone significantly increased over the observation time, while marrow areas decreased. There was no statistically significant difference in the amount of new bone formation between the Bio-Oss group (new bone 29.52% ± 7.43%) and the Bio-Oss/autogenous bone group (new bone 32.23% ± 6.86%). In the 4 patients treated with autogenous bone alone, a greater amount of newly formed bone was found; however, in these cases the area volume filled was smaller than in the other 2 groups. Discussion: The data showed that new bone formation takes place up to 8 months after sinus floor elevation and that there is no difference in the amount of bone formation between procedures done with the bone substitute alone or with the mixture of the substitute and autogenous bone. Conclusion: These data suggest that predictable bone formation can be achieved with the use of Bio-Oss.