Background Colorectal cancer (CRC) is an ideal disease for screening due to known and detectable precursor lesions and slow progression from benign adenoma to invasive cancer. The introduction of organized population-based screening programs reduces the burden of colorectal cancer and increases the quality of the screening process with a more favorable harm to benefit ratio compared to opportunistic screening. MethodsThe study used the microsimulation screening analysis-colon simulation model for the estimation of the effect of various factors on cancer incidence and mortality. The model simulated the Slovakian population from 2018 to 2050. Study includes the analysis of two screening strategies the fecal immunochemical test (FIT) every 2 years and annual FIT. Cost-effectiveness parameters were evaluated comparing each simulated screening scenario with no screening. ResultsCompared to no screening, the biennial FIT would detect 29 600 CRC cases and annual FIT 37 800 CRC cases. Mortality due to CRC showed benefits for both strategies with 17,38% reduction in biennial FIT and 24,67% reduction in annual FIT approach. Both screening programs were more costly as well as more effective compared to no screening. The ICER for biennial FIT strategy was 1776 EUR per 1 QALY and for the annual FIT 3991 EUR per 1 QALY. ConclusionsIn summary, this is the first costeffectiveness analysis focusing on multiple national CRC screening strategies in Slovakia. Both strategies demonstrated cost-effectiveness compared to no screening. However, for optimal population-based programmatic screening strategy, the policymakers should also consider human resources availability, acceptability of screening test among the population or additional resources including the screening funding.