Background: Several colorectal cancer-screening tests are available, but it is uncertain which provides the best balance of risks and benefits within a screening programme. We evaluated cost-effectiveness of a population-based screening programme in Ireland based on (i) biennial guaiac-based faecal occult blood testing (gFOBT) at ages 55-74, with reflex faecal immunochemical testing (FIT); (ii) biennial FIT at ages 55-74; and (iii) once-only flexible sigmoidoscopy (FSIG) at age 60.Methods:A state-transition model was used to estimate costs and outcomes for each screening scenario vs no screening. A third party payer perspective was adopted. Probabilistic sensitivity analyses were undertaken.Results:All scenarios would be considered highly cost-effective compared with no screening. The lowest incremental cost-effectiveness ratio (ICER vs no screening \[euro]589 per quality-adjusted life-year (QALY) gained) was found for FSIG, followed by FIT (\[euro]1696) and gFOBT (\[euro]4428); gFOBT was dominated. Compared with FSIG, FIT was associated with greater gains in QALYs and reductions in lifetime cancer incidence and mortality, but was more costly, required considerably more colonoscopies and resulted in more complications. Results were robust to variations in parameter estimates.Conclusion:Population-based screening based on FIT is expected to result in greater health gains than a policy of gFOBT (with reflex FIT) or once-only FSIG, but would require significantly more colonoscopy resources and result in more individuals experiencing adverse effects. Weighing these advantages and disadvantages presents a considerable challenge to policy makers. © 2012 Cancer Research UK All rights reserved.