BackgroundContrast agent-enhanced digital mammography (CEDM) has been shown to be more sensitive and specific than two-dimensional full-field digital mammography in the diagnostic setting. Few studies have reported on its performance in the screening setting.PurposeTo evaluate the performance of CEDM for breast cancer screening.Materials and MethodsThis retrospective study included women who underwent dual-energy CEDM for breast cancer screening from December 2012 through April 2016. Medical records were reviewed for age, risk factors, short-interval follow-up and biopsies recommended, and cancers detected. Sensitivity, specificity, positive predictive value of abnormal findings at screening (PPV1), positive predictive value of biopsy performed (PPV3), and negative predictive value were determined.ResultsIn the study period 904 baseline CEDMs were performed. Mean age was 51.8 years ± 9.4 (standard deviation). Of 904 patients, 700 (77.4%) had dense breasts, 247 (27.3%) had a family history of breast cancer in a first-degree relative age 50 years or younger, and 363 (40.2%) a personal history of breast cancer. The final Breast Imaging Reporting and Data System score was 1 or 2 in 832 of 904 (92.0%) patients, score of 3 in 25 of 904 (2.8%) patients, and score of 4 or 5 in 47 of 904 (5.2%) patients. By using CEDM, 15 cancers were diagnosed in 14 of 904 women (cancer detection rate, 15.5 of 1000). PPV3 was 29.4% (15 of 51). At least 1-year follow up was available in 858 women. There were two interval cancers. Sensitivity was 50.0% (eight of 16; 95% confidence interval [CI]: 24.7%, 75.3%) on the low-energy images compared with 87.5% (14 of 16; 95% CI: 61.7%, 98.4%) for the entire study (low-energy and iodine images; P = .03). Specificity was 93.7% (789 of 842; 95% CI: 91.8%, 95.2%); PPV1 was 20.9% (14 of 67; 95% CI: 11.9%, 32.6%), and negative predictive value was 99.7% (789 of 791; 95% CI: 99.09%, 99.97%).ConclusionContrast-enhanced digital mammography is a promising technique for screening women with higher-than-average risk for breast cancer.© RSNA, 2019.