Background & Aims: Diminutive adenomas (1-9 mm in diameter) are frequently found during colon cancer screening with flexible sigmoidoscopy (FS). This trial assessed the predictive value of these diminutive adenomas for advanced adenomas in the proximal colon. Methods: In a multicenter, prospective cohort trial, we matched 200 patients with normal FS and 200 patients with diminutive adenomas on FS for age and gender. All patients underwent colonoscopy. The presence of advanced adenomas (adenoma ≥ 10 mm in diameter, villous adenoma, adenoma with high grade dysplasia, and colon cancer) and adenomas (any size) was recorded. Before colonoscopy, patients completed questionnaires about risk factors for adenomas. Results: The prevalence of advanced adenomas in the proximal colon was similar in patients with diminutive adenomas and patients with normal FS (6% vs. 5.5%, respectively) (relative risk, 1.1; 95% confidence interval [Cl], 0.5-2.6). Diminutive adenomas on FS did not accurately predict advanced adenomas in the proximal colon: sensitivity, 52% (95% Cl, 32%-72%); specificity, 50% (95% Cl, 49%-51%); positive predictive value, 6% (95% Cl, 4%-8%); and negative predictive value, 95% (95% Cl, 92%-97%). Male gender (odds ratio, 1.63; 95% Cl, 1.01-2.61) was associated with an increased risk of proximal colon adenomas. Conclusions: Diminutive adenomas on sigmiodoscopy may not accurately predict advanced adenomas in the proximal colon.