Aims: Screening colonoscopy’s effectiveness in reducing risk of death from right colon cancers remains unclear. Methodological challenges of existing observational studies addressing this issue motivated the design of ‘Effectiveness of Screening for Colorectal Cancer in Average-Risk Adults (SCOLAR)’. Methods: SCOLAR is a nested case–control study based on two large integrated health systems. This affords access to a large, well-defined historical cohort linked to integrated data on cancer outcomes, patient eligibility, test indications and important confounders. Results: We found electronic data adequate for excluding ineligible patients (except family history), but not the detailed information needed for test indication assignment. Conclusion: The lessons of SCOLAR’s design and implementation may be useful for future studies seeking to evaluate the effectiveness of screening tests in community settings.