To compare reader ratings of the clinical diagnostic quality of 50 and 100 μm computed radiography (CR) systems with screen-film mammography (SFM) in operative specimens.Mammograms of 57 fresh operative breast specimens were analysed by 10 readers. Exposures were made with identical position and compression with three mammographic systems (Fuji 100CR, 50CR and SFM). Images were anonymised and readers blinded to the CR system used. A five-point comparative scoring system (-2 to +2) was used to assess seven quality criteria and overall diagnostic value. Statistical analysis was subsequently performed of reader ratings (n = 16,925).For most quality criteria, both CR systems were rated as equivalent to or better than SFM. The CR systems were significantly better at demonstrating skin edge and background tissue (p < 1 × 10(-5)). Microcalcification was best demonstrated on the CR50 system (p < 1 × 10(-5)). The overall diagnostic value of both CR systems was rated as being as good as or better than SFM (p < 1 × 10(-5)).In this clinical setting, the overall diagnostic performance of both CR systems was as good as or better than SFM, with the CR50 system performing better than the CR100.