Objectives <p>Cone beam computed tomography (CBCT) provides morphological details of the dental hard tissues and bone. However, the relationship between object density and CBCT grey values is unreliable and limits application of CBCT for quantitative evaluation of bone density. This single center, open-label clinical trial investigated the validity of novel dual-energy CBCT device (DE-CBCT) to assess jaw bone density.</p> Methods <p>The study analyses comprised 24 subjects who were examined with DE-CBCT and multidetector CT (MDCT)—an established standard for bone density assessment. MDCT and DE-CBCT scans of each subject were analyzed in the vendor’s software application for assessment of bone density at 10 discrete sites in the jaws. Two independent assessments were made.</p> Results <p>The mean bone density assessed by DE-CBCT and MDCT were not significantly different (0.46 ± 0.36&#xa0;g/cc versus 0.48 ± 0.31&#xa0;g/cc, respectively). Bone density assessments from DE-CBCT correlated well with MDCT assessments (Pearson’s correlation <i>r</i> = 0.92, <i>p</i> &lt; 0.0001). Bland-Altman analyses demonstrated higher agreement between the two techniques at densities great than 0.6&#xa0;g/cm³. However, at lower densities the limits of agreement were broad.</p> Conclusions <p>DE-CBCT is a promising approach to assess bone density in the jaw bones. The investigational device performs best in well-trabeculated and cortical bone, with reduced reliability in sparsely trabeculated regions. Future refinements in this technology will be needed to expand the range of reliability for reliable assessment of bone density.</p> Clinical trials registration <p>The study is registered in clinical trials.gov, NCT04686084.</p>