Skeletal assessment by morphometry at peripheral sites (e.g. metacarpal index), although simple to perform and widely available, was limited by poor precision and technical aspects of radiogrammetry. Digital X-ray radiogrammetry (DXR) uses the principles of this long-established method but applies more sophisticated methodology to overcome these problems. The aims of this study were to (a) investigate the effects of radiographic technique on bone mineral density (BMD) measurement by DXR, (b) compare DXR to dual-energy X-ray absorptiometry (DXA) and single-energy X-ray absorptiometry (SXA) and (c) determine the applicability of DXR in identifying individuals who most appropriately might be referred for axial DXA. Different radiographers performing the radiograph do not adversely affect precision. Precision, unstandardised (CV%) and standardised (sCV%), is good with both double (DF)- and single (SF)-sided emulsion radiographic film, but better with SF (CV% 0.92 vs 1.12 DF; SCV% 1.76 vs 2.93 DF). Repeat analysis precision was determined on SF (CV% 0.24, sCV% 0.55). A significant ( p<0.001), systematic difference was found between BMD measured from DF and SF (mean difference 0.017 g/cm(2)). The overall percentage difference between the methods was 2.98% (range 0.18-5.78%). Correlations between DXR BMD and DXA were moderately good (r=0.56-0.77, p<0.001); with SXA of the forearm they were excellent (r=0.91, p<0.001). The sensitivity and specificity of DXR for detecting women with osteopaenia or osteoporosis (DXA T-score less than -1; World Health Organisation) was determined at the spine [area under curve (AUC)=0.82, standard error (SE)=0.04], femoral neck (AUC=0.84, SE=0.04) and total hip (AUC=0.84, SE=0.04). Based on femoral neck BMD for detection of osteopaenia, a DXR T-score threshold of -1.05 would be appropriate for detection of patients who might benefit most from axial DXA measurements. The DXR is quick and simple to use, having potential for application in a variety of settings as analysis can be performed in a central unit, with radiographs taken in sites over a wide geographical area. Retrospective analysis may also be performed, e.g. on radiographs taken to monitor rheumatoid arthritis. The technique may also provide a simple, widely available and relatively inexpensive method to assess patients at risk of osteopaenia or osteoporosis, and who most appropriately could be referred for axial DXA. This may be particularly relevant in those who suffer low-trauma fractures and attend accident and emergency or fracture clinics, where investigation for osteoporosis is often overlooked.