Purpose: To evaluate the clinical effectiveness and cost-effectiveness of screening strategies in which MR imaging and screen-film mammography were used, alone and in combination, in women with BRCA1 mutations. Materials and Methods: Because this study did not involve primary data collection from individual patients, institutional review board approval was not needed. By using a simulation model, we compared three annual screening strategies for a cohort of 25-year-old BRCA1 mutation carriers, as follows: (a) screen-film mammography, (b) MR imaging, and (c) combined MR imaging and screen-film mammography (combined screening). The model was used to estimate quality-adjusted life-years (QALYs) and lifetime costs. Incremental cost-effectiveness ratios were calculated. Input parameters were obtained from the medical literature, existing databases, and calibration. Costs (2007 U.S. dollars) and quality-of-life adjustments were derived from Medicare reimbursement rates and the medical literature. Sensitivity analysis was performed to evaluate the effect of uncertainty in parameter estimates on model results. Results: In the base-case analysis, annual combined screening was most effective (44.62 QALYs), and had the highest cost ($110973), followed by annual MR imaging alone (44.50 QALYs, $108641), and annual mammography alone (44.46 QALYs, $100336). Adding annual MR imaging to annual mammographic screening cost $69125 for each additional QALY gained. Sensitivity analysis indicated that, when the screening MR imaging cost increased to $960 (base case, $577), or breast cancer risk by age 70 years decreased below 58% (base case, 65%), or the sensitivity of combined screening decreased below 76% (base case, 94%), the cost of adding MR imaging to mammography exceeded $100000 per QALY. Conclusion: Annual combined screening provides the greatest life expectancy and is likely cost-effective when the value placed on gaining an additional QALY is in the range of $50000-$100000. (c) RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09091086/-/DC1.