Background: Colorectal cancer (CRC) is one of the leading causes of cancer mortality in Belgium. In Flanders (Belgium), a population-based screening program with a biennial immunochemical faecal occult blood test (iFOBT) in women and men aged 56-74 has been organised since 2013. This study assessed the cost-effectiveness and budget impact of the colorectal population-based screening program in Flanders (Belgium). Methods: A health economic model was conducted, consisting of a decision tree simulating the screening process and a Markov model, with a time horizon of 20 years, simulating natural progression. Predicted mortality and incidence, total costs, and quality-adjusted life-years (QALYs) with and without the screening program were calculated in order to determine the incremental cost-effectiveness ratio of CRC screening. Deterministic and probabilistic sensitivity analyses were conducted, taking into account uncertainty of the model parameters. Results: Mortality and incidence were predicted to decrease over 20 years. The colorectal screening program in Flanders is found to be cost-effective with an ICER of 1681/QALY (95% CI -1317 to 6601) in males and (sic)4,484/QALY (95% CI -3254 to 18,163). The probability of being cost-effective given a threshold of (sic)35,000/QALY was 100% and 97.3%, respectively. The budget impact analysis showed the extra cost for the health care payer to be limited. Conclusion: This health economic analysis has shown that despite the possible adverse effects of screening and the extra costs for the health care payer and the patient, the population-based screening program for CRC in Flanders is cost-effective and should therefore be maintained. (C) 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.