Background: The vigilance decrement and prevalence effect both describe changes to speed and accuracy with time on task. Whilst there is much laboratory based research on these effects, little is known about whether they occur in real world mammography practice. Methods: The Changing Case Order to Optimise Patterns of Performance in Screening (CO-OPS) trial randomised 37,724 batches containing 1.2 million women attending breast screening to intervention or control (222,208 from the Midlands of England). In the control arm the batch was examined in the same order by both readers, in the intervention arm it was examined in a different order by both readers. Time taken, recall decision by both readers, and cancers detected were recorded for each case, and used to examine patterns of performance with time on task. Results: 49,575 women were recalled and 10,484 had cancer detected. Median time taken to examine each case was 35 seconds (out of cases where time taken was 10 minutes or less). The intervention did not affect overall cancer detection rates or recall rates. A more detailed analysis of the Midlands data indicates cancer detection rate did not change when reading up to 60 cases in a batch, but recall rate reduced. Time taken per case reduced with time on task, from a median 41 seconds when examining the second case in the batch to 28.5 seconds examining the 60th case. Conclusion: Reader behavior and performance systematically changes with time on task in breast screening.