OBJECTIVES: To conduct a cost-effectiveness analysis to evaluate whether the addition of a fecal occult blood test (FOBT) kit to a mailed invitation for recall compared to a mailed invitation for recall alone increases participation among patients who had responded previously to a mailed invitation in screening for colorectal cancer (CRC). METHODS: The perspective of the analysis will be that of the cancer agency in Ontario, Canada. Eligible patients (responders to the initial pilot study invitation, FOBT negative, and now due for repeat screening) from 61 physicians were randomly allocated to one of the two interventions: (1) Mailed FOBT kit and mailed invitation for recall from their family physician (intervention group) OR (2) mailed invitation alone for recall (control group). Health system and program resources and costs associated with each group will be identified and quantified. Resources will be stratified into fixed costs (initial set-up costs including document development, programming for ongoing maintenance, etc.), variable or recurrent costs (costs of the kit, administrative costs, physician visits etc.) and staff costs (call centre support personnel and business analyst).  RESULTS: There are a total of 431 patients in the intervention group and 452 patients in the control group. Overall costs for each group will be determined, and the cost per patient will be reported. Cost drivers will be identified by conducting a series of univariate sensitivity analyses, including reducing the cost of the kit and using different assumptions for kit wastage. The results will show whether the addition of the FOBT kit to the mailed invitation is cost effective when compared to a mailed invitation only.  CONCLUSIONS: This cost effectiveness analysis will help in determining effective strategies for screening programs that are needed to reduce CRC mortality at a population level.