OBJECTIVES: More than one million new cases of colorectal cancer are diagnosed worldwide annually. In Ireland, incidence rates are among the highest in western Europe, survival is lower than the European average, and mortality in men exceeds that in other western European countries. We evaluated the cost-effectiveness of a population-based colorectal cancer screening programme in Ireland. METHODS: Three screening scenarios were assessed: 1) biennial guaiac-based faecal occult blood testing (gFOBT) in those aged 55-74; 2) biennial faecal immunochemical testing (FIT) in those aged 55-74; and 3) once-only flexible sigmoidoscopy (FSIG) at age 60. A Markov model was used to followed a cohort of 55-year-old individuals over their lifetime. Model parameters were obtained from local data, literature review and expert clinical opinion. Costs included screening and diagnostic tests, cancer treatment, complications, and surveillance of screen-detected adenomas. Health outcomes were assessed in quality-adjusted life years (QALYs). Costs and outcomes were discounted at 4% per annum.  Screening scenarios were compared with the status quo ("no screening"). Probabilistic sensitivity analyses were undertaken. RESULTS: All three screening scenarios were highly cost-effective compared to no screening. In the base-case analysis, FSIG had the lowest incremental cost-effectiveness ratio (ICER=€589 per QALY gained), followed by FIT (€1,696 per QALY gained), and gFOBT (€4428 per QALY gained). gFOBT was dominated. Compared to FSIG, FIT was associated with a greater health gain, and greater lifetime reductions in colorectal cancer incidence (15%) and mortality (36%).  However, it was more costly than FSIG, required more colonoscopies, and would result in more complications. The ICER for FIT versus FSIG was €2058 per QALY gained.  Results were robust to variations in parameter estimates. CONCLUSIONS: These results suggest that population-based colorectal cancer screening would be a highly cost-effective in Ireland. FIT is the optimal screening strategy since it as associated with the greatest health gain.