OBJECTIVE. The purpose of this study is to compare the diagnostic performance of screening digital breast tomosynthesis (DBT) to that of full-field digital mammography (FFDM) in a mixed DBT and FFDM imaging environment. MATERIALS AND METHODS. This retrospective observational study consisted of all female patients undergoing screening DBT or FFDM at an academic medical center and outpatient imaging facility between October 2012 and May 2015. Patient demographics and personal history of breast cancer were collected from the electronic medical record. A natural language processing algorithm extracted patients' breast density, current or prior imaging findings, and BI-RADS category from their most recent prior imaging examinations. To control for differential selection of FFDM versus DBT, we applied propensity score matching based on patient age, imaging site, and prior imaging findings. An institutional breast cancer registry identified cancer diagnoses. Primary outcomes of recall rate, cancer detection rate, and positive predictive value 1 (PPV1) were compared between matched FFDM and DBT groups. RESULTS. Among 68,794 screening examinations, we matched 16,264 FFDM with 21,074 DBT examinations (total, 37,338 examinations) using nearest neighbor propensity score matching. Recall rates were 10.3% (1683/16,264) for FFDM and 10.7% (2254/21,074) for DBT (p = 0.26). Cancer detection rates (number of cancers/1000 examinations) were 1.8/1000 for FFDM and 3.8/1000 for DBT (p = 0.005). The PPV1 (number of cancers/number of recalls) was 1.8% (26/1478) for FFDM and 3.6% (37/1036) for DBT (p = 0.006). CONCLUSION. FFDM and DBT recall rates were not significantly different in a mixed FFDM and DBT breast imaging practice. However, the PPV1 of recalled cases and the cancer detection rate (the primary screening objective) were significantly higher with DBT compared with FFDM.