Background. Oral alendronate, risedronate, and raloxifene are effective treatment options in the management of postmenopausal osteoporosis. There is little previously reported about the renal safety profiles of these three agents in osteoporosis. We aimed to assess the risk of renal toxicity associated with oral alendronate, risedronate, and raloxifene in the treatment of osteoporosis, prospectively. Methods. One hundred and twentyseven patients with osteoporosis and osteopenia according to lumbar or femoral-neck bone mineral density t score were enrolled in the study. The patients were randomized to alendronate 70 mg once weekly (n = 47), risedronate 35 mg once weekly (n = 44), or raloxifene 60 mg per day (n = 36) for one year. Preliminary screening included medical history, physical examination, lumbar and femoral bone mineral densitometry measurement, and blood biochemical tests, including renal function tests. The biochemical markers were then assessed at the end of 12 months. Results. There was no significant difference between basal and final renal function parameters of each group. Also these parameters did not differ between the three groups after 12 months of treatment period. Conclusions. These results demonstrate that alendronate, risedronate, and raloxifene are all safe drugs for renal functions in the treatment of osteoporosis.