Background: Comparing the cost-effectiveness of various antiosteoporotic drugs has not been defined. Methods: We determined the cost-effectiveness of calcitonin, raloxifene, bisphosphates and PTH in a base-case cohort of women aged 65 or older with osteoporosis. After bone densitometry, women were stratified into groups of treatment or no treatment. Our outcome goal was a value of $100,000 or less per quality-adjusted life years (QALY). A sensitivity analysis varied nonvertebral fracture reduction and compliance between the two most effective strategies to test various cost per QALY thresholds. Results: Bisphosphonates displayed the most favorable incremental cost saving and prevented more fractures in our base-case analysis. In a sensitivity analysis, virtually all values of bisphosphonates were under $100,000 per QALY and parathyroid hormone (PTH) was between $100,000 and $200,000 per QALY. Conclusions: Only bisphosphonates are cost-effective for fracture prevention in osteoporotic women aged 65 or older and this economic advantage is also maintained in subsets who have a lower relative risk of future fracture. Copyright © 2006 by The Southern Medical Association.