Objective To evaluate the cost-effectiveness of different screening strategies for colorectal cancer in Colombia. Methods We designed a Markov model to compare the clinical and economic impact in terms of reducing the incidence and mortality from colorectal cancer (CRC). Six screening strategies for adults were compared: fecal occult blood (FOBT) immunochemical and guaiac type, conventional colonoscopy, flexible sigmoidoscopy, and FOBT guaiac and immunochemical type more sigmoidoscopy. We used the third-party payer perspective, including only direct costs, the time horizon was the life expectancy of the Colombian population. We estimated cost-effectiveness ratios (CERs) and incremental cost-effectiveness (ICER). Were performed deterministic sensitivity analysis and probabilistic. We applied a discount rate of 3% in the costs and health outcomes. Results The screening strategy more cost-effective was the FOBT biennial guaiac type. The cost per life year gained was US$10,347.37, US$18,380.64, and US$45,158.05. For FOBT guaiac biennial, FOBT guaiac annual and FOBT inmunoquímica biennial respectively. The ICER is sensitive to the percentage of false positive test for FOBT guaiac type values greater than 10%, and the cost of the test. Conclusions The screening strategy more cost-effective for Colombia is the FOBT biennial guaiac type, using as a threshold the gross domestic product (GDP) per capita in Colombia.