OBJECTIVE To evaluate the effect of misoprostol on bone mineral density in postmenopausal women. METHODS The study was performed in a randomized controlled prospective manner in 90 women with menopause at Süleymaniye Maternity and Women's Diseases Teaching and Research Hospital between January and December 2003. Cases were divided into three groups each consisting of 30 women who were in menopause for at least 1 year and had t-scores less than -1 by dual energy X-ray densitometry (DEXA). Group I was treated with misoprostol and calcium, Group II received tibolone and calcium and Group III was given calcium only and considered as control group. In all patients, bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle were measured by DEXA and t and z scores were calculated. RESULTS All groups were similar demographically. Bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle in the group treated with misoprostol, increased by 5, 8.1 and 3.6%, respectively. In the tibolone group, bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle increased by 8.3, 5.3 and 7.8%, respectively. There was not a significant difference in t and z-scores and bone mineral density measurements between misoprostol and tibolon groups. CONCLUSIONS Misoprostol may be an alternative treatment for patients with osteopenia and osteoporosis who are not suitable for hormone replacement therapy.