Purpose: To determine the effect of transition to digital screening mammography on clinical outcome measures, including recall rate, cancer detection rate, and positive predictive value (PPV). Materials and Methods: Institutional review board approval and the need for informed consent were waived for this HIPAA-complaint study. Practice audit data were obtained for three breast imaging radiologists from 2004 to 2009. These data were sorted by time period into the following groups: baseline (2004-2005), digital year 1 (2007), digital year 2 (2008), and digital year 3 (2009). The χ2 and Fisher exact tests were used to assess differences in proportions among and between years. Clinical outcomes based on lesion type from 2004 to 2008 were also compared. Computer-aided detection was used. Results: The three radiologists interpreted 32 600 screen-film mammograms and 33 879 digital mammograms. Recall rates increased from 6.0% at baseline to 7.1% in digital year 1 (P < .0001) and continued to increase in subsequent years to 8.5%. The cancer detection rate increased from 3.3 at baseline to 5.3 in digital year 1 (P =.0061), and it remained higher than that at baseline in subsequent years. PPV after screening mammogaphy (PPV1) increased from 5.6% at baseline to 7.5% in digital year 1 and returned to baseline levels in digital year 3. In contrast, PPV after biopsy (PPV3) decreased from 44.5% at baseline to 30.3% in digital year 3 (P =.0021). From 2004 to 2008, 3444 patients with 3493 lesions were recalled. The percentage of recalls for calcifications increased from 13.8% at baseline to a peak of 23.9% in digital year 1 and 17.9% in digital year 2. Both PPV1 and PPV3 decreased for calcifications after the digital transition. Conclusion: Recall rate and cancer detection rate increase for at least 2 years after the transition to digital screening mammography. PPV3 is significantly reduced after digital transition, primarily in patients with microcalcifications.