Introduction: In most breast screening programmes screen-film mammography (SFM) has been replaced by full-field digital mammography (FFDM). We compared interval cancer characteristics at SFM and FFDM screening mammography. Patients and methods: We included all 297 screen-detected and 104 interval cancers in 60,770 SFM examinations and 427 screen-detected and 124 interval cancers in 63,182 FFDM examinations, in women screened in the period 2008-2010. Breast imaging reports, biopsy results and surgical reports of all cancers were collected. Two radiologists reviewed prior and diagnostic mammograms of all interval cancers. They determined breast density, described mammographic abnormalities and classified interval cancers as missed, showing a minimal sign abnormality or true negative. Results: The referral rate and cancer detection at SFM were 1.5% and 4.9 parts per thousand respectively, compared to 3.0% (p <0.001) and 6.6 parts per thousand (p <0.001) at FFDM. Screening sensitivity was 74.1% at SFM (297/401, 95% confidence interval (CI) = 69.8-78.4%) and 77.5% at FFDM (427/551, 95% CI = 74.0-81.0%). Significantly more interval cancers were true negative at prior FFDM than at prior SFM screening mammography (65.3% (81/124) versus 47.1% (49/104), p = 0.02). For interval cancers following SFM or FFDM screening mammography, no significant differences were observed in breast density or mammographic abnormalities at the prior screen, tumour size, lymph node status, receptor status, Nottingham tumour grade or surgical treatment (mastectomy versus breast conserving therapy). Conclusion: FFDM resulted in a significantly higher cancer detection rate, but sensitivity was similar for SFM and FFDM. Interval cancers are more likely to be true negative at prior FFDM than at prior SFM screening mammography, whereas their tumour characteristics and type of surgical treatment are comparable.