Objectives The aim of this study was to evaluate the detection rate and diagnostic performance of 2-dimensional synthetic mammography (SM) as an adjunct to wide-angle digital breast tomosynthesis (WA-DBT) compared with digital mammography (DM) alone or to DM in combination with WA-DBT. Materials and Methods There were 205 women with 179 lesions included in this retrospective reader study. Patients underwent bilateral, 2-view (2v) DM and WA-DBT between March and June 2015. The standard of reference was histology and/or 1-year stability at follow-up. Four blinded readers randomly evaluated images according to the BI-RADS lexicon from 3 different protocols: 2v DM alone, 2v DM with 2v WA-DBT, and 2v SM with 2v WA-DBT. Detection rate, sensitivity, specificity, and accuracy were calculated and compared using multivariate analysis. Readers' confidence and image quality were evaluated. Results The detection rate ranged from 68.7% to 79.9% for DM, 76.5% to 84.4% for DM with WA-DBT, and 73.2% to 84.9% for SM with WA-DBT. Sensitivity and accuracy were significantly higher when DBT was available (P
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