A simple questionnaire would be useful to identify individuals most in need of bone mineral density (BMD) testing. We designed a new predictive model and risk assessment instrument based on an extensive review of the literature evaluating risk factors for osteoporosis, and tested its performance in a large cohort of postmenopausal women in whom BMD was measured by dual x-ray absorptiometry. In total, 1303 postmenopausal women from an outpatient osteoporosis clinic participated in this study. The Osteoporosis Index of Risk (OSIRIS) is based on four variables: age, body weight, current hormone replacement therapy use and history of previous low impact fracture. The sensitivity and specificity for an OSIRIS value of +1 were respectively 78.5% and 51.4%. The AUC under the ROC curve of OSIRIS was 0.71. Three categories were arbitrarily created using OSIRIS, with cutoff of +1 and -3. The low risk category (OSIRIS > +1) represented 41% of all women; only 7% of the women in this category had osteoporosis. The prevalence of osteoporosis was very high (66%) among the group at high risk (OSIRIS < -3 representing 15% of all women). The prevalence of osteoporosis was 39% in the intermediate risk group (-3 < OSIRIS < +1, 44% of all women). In conclusion, OSIRIS is a simple index based on four easy-to-collect variables from postmenopausal women, it shows a high degree of accuracy, and performed well for classifying the degree of risk of osteoporosis in western European women of Caucasian lineage. Based on this instrument it is possible to propose a strategy that would initiate treatment in women with very high risk, postpone BMD measurement in women with low risk and limit BMD measurement to women with intermediate risk of osteoporosis, this would spare more than 55% of the densitometry bill compared with a mass screening scenario.