To evaluate bone regeneration in a heterogenous, deproteinized bone mineral (DBM) when used as an onlay graft. In this study, eight rabbits received two titanium bone graft holders (TBGHs), one on the left and one on the right lateral surface of the mandible. Each TBGH possessed two cylindrical chambers, which were perforated with numerous sub-millimeter pores. On the experimental side of the jaw, the chambers were filled with DBM particles (Bio-Oss®, Geistlich Pharmaceutical AG, Walhusen, Switzerland). Chambers on the opposite (control) side of the jaw were empty (no DBM). Following TBGH placement both the control and experimental TBGHs were covered with a barrier layer of collagen membrane (Bio-Gide®, Geistlich Pharmaceutical AG, Walhusen, Switzerland). After twelve weeks, sections of the mandible were harvested for radiographic and histomorphometric evaluation. New bone formation was seen in both test and control chambers. However, the newly generated bone was greater in the experimental (DBM) group (18.41%) than in the control group (5.31%). The difference was statistically significant (p < 0.001). Upon quantification of the radio-dense area from the radiographs, there was significantly more bone and/or graft in the experimental group (12.96 mm2 ± 1.48) than the control group (8.59 mm2 ± 3.54) (p < 0.001). Similarly, the DBM chambers were filled to a significantly greater height (2.73 mm ± 0.24) than the control chambers (1.83 mm ± 0.72) (p < 0.001). DBM can enhance greater new bone formation when used as an onlay graft, underneath a rigid barrier.