BACKGROUND: Computer-aided mammography is rapidly gaining clinical acceptance, but few data demonstrate its actual benefit in the clinical environment. We assessed changes in mammography recall and cancer detection rates after the introduction of a computer-aided detection system into a clinical radiology practice in an academic setting. METHODS: We used verified practice- and outcome-related databases to compute recall rates and cancer detection rates for 24 Mammography Quality Standards Act-certified academic radiologists in our practice who interpreted 115,571 screening mammograms with (n = 59,139) or without (n = 56,432) the use of a computer-aided detection system. All statistical tests were two-sided. RESULTS: For the entire group of 24 radiologists, recall rates were similar for mammograms interpreted without and with computer-aided detection (11.39% versus 11.40%; percent difference = 0.09, 95% confidence interval [CI] = -11 to 11; P =.96) as were the breast cancer detection rates for mammograms interpreted without and with computer-aided detection (3.49% versus 3.55% per 1000 screening examinations; percent difference = 1.7, 95% CI = -11 to 19; P =.68). For the seven high-volume radiologists (i.e., those who interpreted more than 8000 screening mammograms each over a 3-year period), the recall rates were similar for mammograms interpreted without and with computer-aided detection (11.62% versus 11.05%; percent difference = -4.9, 95% CI = -21 to 4; P =.16), as were the breast cancer detection rates for mammograms interpreted without and with computer-aided detection (3.61% versus 3.49% per 1000 screening examinations; percent difference = -3.2, 95% CI = -15 to 9; P =.54). CONCLUSION: The introduction of computer-aided detection into this practice was not associated with statistically significant changes in recall and breast cancer detection rates, both for the entire group of radiologists and for the subset of radiologists who interpreted high volumes of mammograms.