High-resolution 3D bone-tissue structure measurements may provide information critical to the understanding of the bone regeneration processes and to the bone strength assessment. Tissue engineering studies rely on such nondestructive measurements to monitor bone graft regeneration area. In this study, we measured bone yield, fractal dimension and trabecular thickness through micro-CT slices for different grafts and controls. Eight canines underwent surgery to remove a bone volume (defect) in the canine’s jaw at a total of 44 different locations. We kept 11 defects empty for control and filled the remaining ones with three regenerative materials; NanoGen (NG), a FDA-approved material (n=11), a novel NanoCalcium Sulfate (NCS) material (n=11) and NCS alginate (NCS+alg) material (n=11). After a minimum of four and eight weeks, the canines were sacrificed and the jaw samples were extracted. We used a custom-built micro-CT system to acquire the data volume and developed software to measure the bone yield, fractal dimension and trabecular thickness. The software used a segmentation algorithm based on histograms derived from volumes of interest indicated by the operator. Using bone yield and fractal dimension as indices we are able to differentiate between the control and regenerative material (p<0.005). Regenerative material NCS showed an average 63.15% bone yield improvement over the control sample, NCS+alg showed 55.55% and NanoGen showed 37.5%. The bone regeneration process and quality of bone were dependent upon the position of defect and time period of healing. This study presents one of the first quantitative comparisons using non-destructive Micro-CT analysis for bone regenerative material in a large animal with a critical defect model. Our results indicate that Micro-CT measurement could be used to monitor in-vivo bone regeneration studies for greater regenerative process understanding.