Background Few results are available about subsequent outcomes after screening with digital breast tomosynthesis (DBT). Purpose To compare the diagnostic accuracy of a screening round with DBT plus synthetic mammography (SM) (hereafter, DBT+SM) and the repeat screening round with DBT with SM (hereafter, DBT+SM) or full-field digital mammography (FFDM) with FFDM screening. Materials and Methods This prospective study (Verona Pilot Study, clinical trial identification: 2015/1238) included women screened with DBT+SM between April 2015 and March 2017 and rescreened with DBT+SM or FFDM between April 2017 and March 2019. Screening performance (recall rate, cancer detection rate [CDR], and positive predictive value of recall [PPV1]) was compared with that obtained from 28 680 women screened with FFDM between 2013 and 2014 (control group). Cancer stages were compared between modalities and screening rounds. A χ2 test was used to evaluate differences. P < .05 was indicative of a statistically significant difference. Results Of 34 638 women enrolled, 32 870 (median age, 58 years; age range, 52-71 years) underwent repeat screening-16 198 with DBT+SM and 16 672 with FFDM. The CDR was higher for repeat screening with DBT+SM than for the control group with FFDM (8.1 per 1000 women screened vs 4.5 per 1000 women screened, respectively; P < .01) and was not significantly lower for repeat screening with FFDM (3.5 per 1000 women screened vs 4.5 per 1000 women screened, respectively; P = .11). Compared with the control group, there was no difference in the recall rate at repeat screening with both DBT+SM (3.71% vs 3.40%, respectively; P = .10) and FFDM (3.71% vs 3.69%, P = .92), whereas PPV1 was higher only when repeat screening was performed with DBT+SM (23.8% vs 12.0%, P < .01). At repeat screening, the proportion of cancers stage II or higher was 14.5% (19 of 131 cancers) with DBT+SM and 8.5% (five of 59 cancers) with FFDM, both of which were lower than the proportion in the control group with FFDM (30 of 110 cancers, 27.3%) (P ≤ .01). Conclusion At repeat screening, digital breast tomosynthesis plus synthetic mammography depicted more cancers than full-field digital mammography (FFDM) and found a lower number of stage II cancers compared with FFDM. © RSNA, 2020 See also the editorial by Bae in this issue.