Although digital breast tomosynthesis (DBT) may be an effective breast cancer screening modality, alternatives are important to explore as this technique presents some challenges for population screening implementation. To compare the detection performance of three-view (craniocaudal [CC] + mediolateral oblique [MLO] + mediolateral/lateromedial [ML/LM]) digital mammography (DM) to two-view (CC + MLO) DBT. In this institutional review board-approved study, recalled screening DBT exams from 3 March 2014 to 31 March 2015 with a ML/LM view acquired within 30 days were retrospectively reviewed for detection of breast cancer. Six radiologists blinded to outcomes evaluated two-view DBT, which included DM and tomosynthesis images, and three-view DM. Probability of malignancy and a BI-RADS score were assigned. Primary outcomes were area under the receiver operating characteristic curve (AUC) and benign and malignant recall rates. The cohort included 121 cases: 37% were malignant and 63% were benign. Reader-averaged AUCs were 0.846 (95% confidence interval [CI] = 0.787-0.905) and 0.853 (95% CI = 0.802-0.904) for three-view DM and DBT, respectively. Benign and malignant recall rates were 53% and 74% for three-view DM and 52% and 75% for DBT, respectively. There was no difference in AUCs ( P = 0.692), and benign ( P = 1) and malignant ( P = 1) recall rates. In this retrospective initial study, the detection performance of two-view DBT and three-view DM were statistically equivalent. Future studies should determine whether three-view DM is a viable alternative to DBT for screening, given its cost and work-flow.