The Province of Liège has conducted an osteoporosis screening strategy for women aged 50 to 69 years. The objective of this study is to investigate the economic characteristics of the screening strategy and to assess its cost-effectiveness, using a Markov microsimulation model. Our analyses suggest that the osteoporosis screening strategy is efficient if the medical community and the patients fulfill the recommendations of the Province of Liège health authorities and if persistence is optimized. Therefore, bone mineral density (BMD) measurement should be performed in all individuals with positive ultrasound screening; individuals having a positive BMD diagnosis should be treated and adherence to therapy should be increased. Furthermore, to improve the efficiency of the screening strategy, we suggest to target screening on women with one or more clinical risk factors, or on women aged 65 years and older.