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Introduction: Although African Americans have the highest colorectal cancer (CRC) incidence and mortality rates of any racial group, their screening rates remain low., Study Design/purpose: This randomized controlled trial compared efficacy of two clinic-based interventions for increasing CRC screening among African American primary care patients., Methods: African American patients from 11 clinics who were not current with CRC screening were randomized to receive a computer-tailored intervention (n = 335) or a non-tailored brochure (n = 358) designed to promote adherence to CRC screening. Interventions were delivered in clinic immediately prior to a provider visit. Univariate and multivariable logistic regression models analyzed predictors of screening test completion. Moderators and mediators were determined using multivariable linear and logistic regression analyses., Results: Significant effects of the computer-tailored intervention were observed for completion of a stool blood test (SBT) and completion of any CRC screening test (SBT or colonoscopy). The colonoscopy screening rate was higher among those receiving the computer-tailored intervention group compared to the nontailored brochure but the difference was not significant. Predictors of SBT completion were: receipt of the computer-tailored intervention; being seen at a Veterans Affairs Medical Center clinic; baseline stage of adoption; and reason for visit. Mediators of intervention effects were changes in perceived SBT barriers, changes in perceived colonoscopy benefits, changes in CRC knowledge, and patient-provider discussion. Moderators of intervention effects were age, employment, and family/friend recommendation of screening., Conclusion: This one-time computer-tailored intervention significantly improved CRC screening rates among low-income African American patients. This finding was largely driven by increasing SBT but the impact of the intervention on colonoscopy screening was strong. Implementation of a CRC screening quality improvement program in the VA site that included provision of stool blood test kits and follow-up likely contributed to the strong intervention effect observed at that site. The trial is registered at ClinicalTrials.gov as NCT00672828., (Copyright © 2021 Elsevier Inc. All rights reserved.)