Background Multiple studies showed digital breast tomosynthesis (DBT) has a higher cancer detection rate and a lower recall rate than full-field digital mammography (FFDM). However, there is a paucity of studies on whether the benign biopsy rate will be lower with DBT. Purpose To evaluate the benign biopsy rate of DBT versus that of FFDM in women recalled after breast screening within the National Health Service Breast Screening Programme. Materials and Methods This prospective single institution study included women who underwent screening FFDM or screening breast MRI between November 13, 2015, and July 29, 2016, and were recalled. Women who were recalled underwent a breast examination, additional imaging (mammography, US), and biopsy, if required. The number of interventions and the outcome of assessment were recorded. FFDM was performed at the screening appointment, and DBT images were acquired when participants attended a screening assessment within 3 weeks after screening FFDM. Two of four readers blinded to biopsy results analyzed DBT images in isolation and then in conjunction with FFDM images and any additional two-dimensional mammographic or US images. Two-tailed McNemar tests were used to test differences in sensitivity and specificity of the two conditions at 5% significance level. Results During the study period, 30 933 women underwent FFDM. A total of 1470 women were recalled (recall rate, 4.8%), and 827 were included after exclusion criteria were applied. Their mean age was 56.7 years ± 7.7 (standard deviation). A total of 145 breast cancers were detected (142 with FFDM, two with DBT only, one with surveillance MRI). Triple assessment without DBT resulted in 571 breast biopsies and enabled detection of 142 cancers. The addition of DBT would have resulted in 298 biopsies and detection of 142 cancers, reducing the number of biopsies from 571 of 827 (69.0%) to 298 of 827 (36.0%). Conclusion When compared with full-field digital mammography, digital breast tomosynthesis can reduce the benign biopsy rate while maintaining the cancer detection rate. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Skaane in this issue.