Abstract To evaluate diagnostic efficacy of deep learning (DL)-based automated bone mineral density (BMD) measurement for opportunistic screening of osteoporosis with routine computed tomography (CT) scans. A DL-based automated quantitative computed tomography (DL-QCT) solution was evaluated with 112 routine clinical CT scans from 84 patients who underwent either chest (N:39), lumbar spine (N:34), or abdominal CT (N:39) scan. The automated BMD measurements (DL-BMD) on L1 and L2 vertebral bodies from DL-QCT were validated with manual BMD (m-BMD) measurement from conventional asynchronous QCT using Pearson’s correlation and intraclass correlation. Receiver operating characteristic curve (ROC) analysis identified the diagnostic ability of DL-BMD for low BMD and osteoporosis, determined by dual-energy X-ray absorptiometry (DXA) and m-BMD. Excellent concordance were seen between m-BMD and DL-BMD in total CT scans (r = 0.961/0.979). The ROC-derived AUC of DL-BMD compared to that of central DXA for the low-BMD and osteoporosis patients was 0.847 and 0.770 respectively. The sensitivity, specificity, and accuracy of DL-BMD compared to central DXA for low BMD were 75.0%, 75.0%, and 75.0%, respectively, and those for osteoporosis were 68.0%, 80.5%, and 77.7%. The AUC of DL-BMD compared to the m-BMD for low BMD and osteoporosis diagnosis were 0.990 and 0.943, respectively. The sensitivity, specificity, and accuracy of DL-BMD compared to m-BMD for low BMD were 95.5%, 93.5%, and 94.6%, and those for osteoporosis were 88.2%, 94.5%, and 92.9%, respectively. DL-BMD exhibited excellent agreement with m-BMD on L1 and L2 vertebrae in the various routine clinical CT scans and had comparable diagnostic performance for detecting the low-BMD and osteoporosis on conventional QCT.