OBJECTIVES: To evaluate the cost-effectiveness of all recommended therapies for prevention of osteoporotic hip, spine, and wrist fractures in postmenopausal women without prior fracture. METHODS: A retrospective, modeled cost-effectiveness analysis of all therapies given in the international guidelines for osteoporosis treatment and prevention of fractures and currently available on the Slovenian market was performed from societal perspective. The analysis included postmenopausal women divided in three age groups treated by the following treatment options: no drug therapy, alendronate, etidronate, calcitonin, hormone replacement therapy (HRT) and raloxifene. Data on clinical efficacy of all therapies in terms of decreasing fracture risk (relative risks for hip, spine and wrist fracture) were pooled from the published summarized systematic reviews of meta-analyses obtained by Medline search. A Markov model of 10-years preventive treatment for women without previous fracture was developed with DATA 4.0 decision analysis software. Model data on baseline fracture and death probabilities were obtained from National Health care Institute 2000 Report. Cost estimates on annual drug treatment and fracture treatment were derived from Slovenian sources (2002 price list) and converted to Euros. Utility values for the health states defined in the model were obtained from the reference literature. RESULTS: The incremental cost-effectiveness ratio for 10 years of HRT treatment versus no therapy ranged from €174088/QALY at age 65-years to €65578/QALY for 75-years and to only €480/QALY at age 85-years, respectively. The incremental cost-effectiveness ratio for 10 years of treatment with alendronate versus no therapy ranged from €183258/QALY at age 65-years to €68457/QALY for 75-years and to only €2291/QALY for age 85-years, respectively. Etidronate, raloxifene, and calcitonin were dominated by either HRT or alendronate for all age groups. CONCLUSIONS: HRT and alendronate can be considered as cost-effective therapies for prevention of osteoporotic fractures in older postmenopausal women without prior fracture.