OBJECTIVES: To assess the cost-effectiveness of an ongoing osteoporosis screening campaign in Belgian women aged from 50 to 69 years. METHODS: A cost-effectiveness analysis was performed using a decision tree analysis and a microsimulation Markov model. We compared the screening campaign versus no intervention. Screening campaign consisted of quantitative ultrasound screening by mobile units. For all individuals having a positive result, three possibilities are observed: no follow-up, direct treatment or screening with DXA (dual energy X-ray absorptiometry). Most of the individuals having a positive DXA result received Alendronate therapy. Sensitivity analyses and simulations were based on model parameters (discount rates, fracture costs, fracture risks, fracture disutility, mortality excess and treatment specificities), characteristics of screening campaign (screening efficacy, prevalence of osteoporosis and screening cost), number of clinical risk factors and persistence level. RESULTS: In the base case (with 100% persistence), the cost per QALY gained for the screening strategy was €44,927. Sensitivity analyses showed that this value was affected by persistence level (€81,921 for realistic persistence). The efficiency greatly improved if we only screen individuals with one clinical risk factor (€23,265) or more (from €15,377 for two clinical risk factors to cost-saving for four clinical risk factors). We also showed that pre-screening using quantitative ultrasound was more efficient than universal DXA screening if the cost of quantitative ultrasound was less than €14.8 per patient screened. CONCLUSION: The base case result was near to threshold value of €45,000 per QALY gained. Consequently, it was difficult to interpret the results and to qualify the campaign efficiency. Our recommendations to improve it are to target screening on individuals with one or more clinical risk factors, to generalize DXA for all individuals having a positive quantitative ultrasound result, to treat all individuals having a positive DXA result and to improve compliance and adherence to therapy.