Alendronate has been proven to be effective in the prevention and treatment of postmenopausal osteoporosis with the recommended daily dose of 10 mg. However, a constraining requirement for dosing limited its general acceptance in treatment. Since alendronate is potent and has a long half-life, weekly administration of alendronate in lower total doses might be safer and more convenient. The purpose of this study was to determine the efficacy of low dose once-weekly 20 mg alendronate in Thai postmenopausal women with osteoporosis. Thirty-nine postmenopausal women with osteoporosis received alendronate 20 mg once a week plus 750 mg elemental calcium daily. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at baseline and 6 and 12 months after treatment. Serum C-terminal telopeptide of type I collagen (CTx-I) was measured by electrochemiluminescence immunoassay at baseline and 3 months after treatment. By the end of 1 year, once weekly 20 mg alendronate significantly increased vertebral BMD (+6.2%, p < 0.001 vs baseline) from baseline whereas there was a reduction of 60.7% in serum CTx-I at 3 months. However, the BMD at femur did not increase significantly (+0.64%). Conclusion. Low-dose intermittent once-weekly 20 mg alendronate was effective, cost saving and had a good safety profile in increasing vertebral BMD and stabilizing BMD at the femoral neck in postmenopausal osteoporosis.