OBJECTIVES: The introduction of digital mammography presents benefits at the technological. However, there are doubts about its impact on the effectiveness of breast cancer screening. The aim of this study was to analyze the cost-effectiveness of the introduction of digital mammography in a population-based breast cancer screening program. METHODS: A discrete-event simulation model was implemented including the processes under a breast cancer screening program and the natural history of breast cancer. The screening events included: invitation (biennial) of the target population (women aged 50-69 years), participation, screening test, confirmatory tests after a positive mammography result, cancer diagnosis and treatment. Natural history of breast cancer included the following health states: no cancer, pre-clinical (non symptomatic) cancer, clinical (or symptomatic) cancer and death. Natural history was modeled as time until a change of health state, and health states were managed using attributes in order to condition the sensitivities and specificities of the tests to the current health state of the woman. Interval cancers were also detected according to the health state. Digital and analogical mammography had the same sensitivity, but different specificities were applied according to type of mammography and also initial or successive screening. Cost-effectiveness was calculated under a 20 year screening scenario and 5 simulations. RESULTS: Simulation started with a target population of 28,020 women. Other 29,552 women were enrolled in the target population during the simulated 20 years. This population resulted in 56,136 screening mammograms. The number confirmatory tests needed was 1864 under analogical mammography and 1724 under digital screening. Screen-detected cancers were 344 with analogical screening and 312 with digital screening. The overall ICER was €349.14. CONCLUSIONS: Results suggest that population-based breast cancer screening with digital mammography is cost-effective. It does not improve the results of conventional analogical mammography, but it reduces the cost in confirmatory tests.