Abstract The tools of AI offer promise to uncover and amplify data, previously hidden in images of the human body, and expand the field of radiomics to more accurately predict breast cancer risk across diverse patient populations. Although deep learning products trained to predict mammographic breast density and risk of breast cancer are now available, their performance in routine clinical settings is largely unknown. Since the creation of the Gail model in 1989, risk models have supported risk-adjusted screening and prevention, and their continued evolution has been a central pillar of breast cancer research. Mammographic breast density is now being incorporated into well-established clinical risk models, which are used to determine eligibility for supplemental imaging and other services for patients at increased risk. However, mammographic breast density assessment is subjective and varies widely between and within radiologists. For example, Sprague et al demonstrated considerable variability of qualitative Breast Imaging Reporting and Data System (BI-RADS) density assessments with a range of 6% to 85% of mammograms being assessed as heterogeneously or extremely dense across 83 radiologists. To limit variability and subjectivity, various automated breast density assessment methods were commercially developed, but clinical evaluation has yielded mixed results. Density is only one limited feature of any woman’s mammogram. Deep learning models can operate over the full resolution of mammogram images to assess a patient’s future breast cancer risk. Rather than manually identifying discriminative image patterns, machine learning models can discover these patterns directly from the data. Specifically, models are trained with full resolution mammograms and the outcome of interest, namely whether the patient developed breast cancer within five years from the date of the examination. Our recent work demonstrates that application of novel artificial intelligence applications to imaging data can significantly improve breast density assessment and breast cancer risk prediction. In addition, unlike traditional models, our DL models perform equally well across varied races, ages, and family histories and we have built a clinical platform which is currently in use to support implementation of our density and risk models into routine clinical care. From this clinical platform, we found that use of a deep learning model more accurately predicts mammographic breast density, reducing human variation and “overcalling” of breast density, and can help healthcare systems more appropriately utilize limited supplemental screening resources as well as provide patients with more accurate information regarding their breast density. We have also found a DL breast cancer risk model, generated in routine clinical mammography screening programs, can predict future breast cancer risk and can more accurately identify women who will most benefit from screening mammography. This DL score can be used in diverse clinical settings that currently depend on traditional risk scores, which are at best modest in performance. DL risk scores based on the mammogram alone can inform shared decision making with patients and their healthcare providers regarding more personalized risk reduction and early detection strategies. Citation Format: C Lehman, B Dontchos, LR Lamb./AI [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES7-3.