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Background: To reduce mortality risk, women with a family history of breast cancer are often screened with mammography before 50 years of age. Additional Magnetic Resonance Imaging (MRI) can improve sensitivity. MRI screening is cost-effective for BRCA1/2 mutation carriers. However, for women with a family history of breast cancer without a proven mutation cost-effectiveness is not clear. We evaluated the cost- effectiveness of additional MRI for women with a familial risk in the largest prospective MRI screening study: the Dutch MRI Screening Study (MRISC). Materials & Methods: Between 1999 and 2007 a total of 1597 women (8370 women years at risk) between 25-70 years, with an estimated cumulative lifetime risk of 15-50% for breast cancer participated in the MRISC. Women were screened with clinical breast examination (CBE) every six months and annual mammography and MRI. We calculated the costs per detected breast cancer. In addition, MRISC data were incorporated into a micro simulation screening analysis model: MISCAN. This model simulates screening programs with different screening modalities and time intervals. Different screening schemes were evaluated and the cost per life-year gained (CLYG) estimated. Results: Forty-seven breast cancers, including 9 Ductal Carcinoma in Situ, were detected. Screening with additional MRI leads to a cost per detected breast cancer treated of 101,962. In increasing age-cohorts the cost decreased, probably due to the higher breast cancer incidence. The cost per detected and treated breast cancer in age group 40-50 years doubled in the age group >60 years. We will demonstrate these results more extensively. With MISCAN modeling we predicted that screening with this scheme from age 35 to 60 years reduces breast cancer mortality by 30% at a CLYG of 119,945 (3.5% discounting), compared to 21% estimated mortality reduction at 45,707 CLYG with mammography and CBE alone. Conclusion: Screening with MRI may improve survival for women with familial risk for breast cancer, but is expensive. However, it may be cost-effective for a select group. We will discuss subgroups that may benefit from MRI screening and in which age category MRI was most effective in our study. [ABSTRACT FROM AUTHOR]