The chemopreventive efficacy of aspirin and the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) for colorectal cancer (CRC) has been tested in a multicentre, placebo-controlled trial. Patients identified at colonoscopy as high-risk for CRC (n = 709) from the English Bowel Cancer Screening Programme were randomly allocated to receive daily doses of aspirin, EPA, a combination of both or placebo for 12 months. The primary end point (proportion of patients with any colorectal adenoma) was analysed after 1 year by colonoscopy: no significant differences between the groups were seen. However, evidence from secondary outcomes did show that both aspirin and EPA decreased the recurrence of some adenoma subtypes, measured by adenoma number, suggesting a precision medicine approach to CRC chemoprevention is needed.