Aim: To assess real-life reader performance as a function of both volume of mammograms read and reading experience in a multicentre cohort. Materials and methods: Thirty-seven film readers from the East Midlands Breast Screening Programme had 3 years of consecutive screen reading results available for comparison. Markers of screening performance as the first film reader [cancer detection rates, small cancer detection rates, recall rates, positive predictive value of recall (PPV), and missed cancers] were compared with both volume of films read and years of film reading experience. For reading volume, readers were categorized according to film reading volume over the 3 year period: <15,000 (i.e., on average less than the recommended 5000/year); 15-<20,000; 20-<25,000; and ≥25,000. For years of experience, readers were categorized into the following groups: <5 years, 5-<10 years, 10-<15 years, and 15-<20 years. Results: There was no evidence to suggest a relationship between years of film reading experience and film-reading performance. For reading volume, there was a significant difference in the distribution of cancer-detection rate between the four groups (p = 0.01); however, there was no difference in small cancer-detection rates, missed cancers or PPV. The median cancer detection rate in the high-volume group (≥25,000 mammograms/3 years) was significantly lower than the other groups combined (6.9 per 1000 women screened versus 7.9 per 1000 women screened). The lowest median recall rate was also in the high-volume group, whilst those readers not meeting the NHSBSP minimum requirement had the highest median recall rate; however, there was borderline evidence to suggest a difference in the distribution of recall rates between the four groups. Conclusion: The data from the East Midlands do not provide any evidence for reducing the threshold volume of 5000 cases /year. However, there appears to be an upper limit above which reader performance deteriorates in terms of lower cancer-detection rates. With the imminent expansion of the programme, this has implications for service quality. These higher-volume readers should be encouraged to recall more borderline cases to assessment. Analysis of national data is recommended to further evaluate these findings.