OBJECTIVE. The purpose of this study was to compare the diagnostic accuracy of digital mammography with that of screen-film mammography in concurrent cohorts participating in the same population-based screening program. MATERIALS AND METHODS. In a retrospective study covering 2004-2005, we compared digital with screen-film mammography in two concurrent screening cohorts of women 50-69 years old participating in a screening program operated from mobile units. Each cohort had 14,385 participants matched by age and interpreting radiologist from all participants consecutively registered. We compared recall and cancer detection rates. RESULTS. The recall rate was higher for digital mammography (4.56% vs 3.96%,p 0.01), particularly when clustered microcalcifications were the only finding (1.05% vs 0.41%, p 10-6) and for younger women (50-59 vs 60-69 years, 5.12% vs 4.17%, p = 0.009). The higher recall rate for digital mammography was mainly evident at incidence screening. The recall rate due to poor technical quality was lower with digital mammography (0.27% vs 0.50%, p = 0.002), possibly because real-time feedback was available. The detection rate was higher for digital mammography (0.72% vs 0.58%, p = 0.14), particularly for cancers depicted as clustered microcalcifications (0.26% vs 0. 12%, p = 0.007), in younger (50-59 years) women (0.63% vs 0.42%, p = 0.09), and in denser breasts (1.09% vs 0.53%, p = 0.24). No significant difference was observed in positive predictive value on recall for digital mammography or screen-film mammography. Early cancer (pTis, pT1mic, pT1a) was more frequent in cancer detected with digital mammography than in that detected with screen-film mammography (41.3% vs 27.3%, p = 0.06). CONCLUSION. Digital mammography maybe more effective than screen-film mammography in contemporary screening practice in mobile units. The data indicate that digital mammography depicts more tumors than does screen-film. mammography, especially lesions seen as microcalcifications. The potential association with improved outcome warrants further study.