OBJECTIVES: To evaluate the cost-effectiveness of Magnetic Resonance Image-Guided Focused Ultrasound (MRgFUS) compared to alternative treatment options for uterine fibroids from a US perspective. METHODS: Techniques of decision analysis and data from secondary sources were used to develop and estimate an economic model of the management of uterine fibroids among premenopausal women. Patients in the model are assumed to receive first-line treatment with MRgFUS, myomectomy, uterine artery embolization (UAE), hysterectomy, or pain medication only. Additional rounds of treatment (up to three) for treatment failure or recurrent fibroids also were incorporated in the model. The model predicts total costs and quality-adjusted life years (QALYs) for each strategy over a lifetime horizon. Data on treatment efficacy and safety were obtained from published and unpublished studies. Cost data (2005 US$) were estimated from a large administrative database and supplemented with expert opinion. Analyses incorporated both direct and indirect (lost productivity) costs. RESULTS: UAE was associated with the most discounted QALYs (17.39), followed by MRgFUS (17.36), myomectomy (17.35), hysterectomy (17.18) and pain management (16.70). Pain management was the least costly strategy ($9,200 per patient), followed by hysterectomy ($19,800), MRgFUS ($27,300), UAE ($28,900), and myomectomy ($35,100). Incremental cost-effectiveness ratios (cost per QALY gained) were $21,800 for hysterectomy, $41,400 for MRgFUS, and $54,200 for UAE; myomectomy was both more costly and less effective than MRgFUS and UAE (i.e., dominated). Sensitivity analyses indicated that results are sensitive to MRgFUS recurrence rates and procedure costs as well as assumptions about the quality-of-life decrement following hysterectomy. CONCLUSION: Our findings suggest that, with the exception of myomectomy, currently available treatment options for uterine fibroids (i.e., hysterectomy, UAE, MRgFUS) are in the range of currently accepted criteria for cost-effectiveness. Any of them could be the cost-effective choice, depending on patient preferences and resource availability.