Background: Many expert panels recommend colorectal cancer screening for average-risk asymptomatic individuals older than 50 years of age. Recent studies have found that 24%to 64%of primary care providers use only the digital fecal occult blood test (FOBT) as their primary screening test. The effectiveness of a single digital FOBT is unknown. Objective: To compare the sensitivity and specificity of digital FOBT and the recommended 6-sample at-home FOBT for advanced neoplasia in asymptomatic persons. Design: Prospective cohort study. Setting: 13 Veterans Affairs medical centers. Patients: 3121 asymptomatic patients 50 to 75 years of age. Intervention: 2665 patients had 6-sample at-home FOBT and digital FOBT, followed by complete colonoscopy. Measurements: We measured the sensitivity of digital and 6-sample FOBT for advanced neoplasia and the specificity for no neoplasia. We calculated predictive values and likelihood ratios for advanced neoplasia, defined as tubular adenomas 10 mm or greater, adenomas with villous histology or high-grade dysplasia, or invasive cancer. Results: Of all participants, 96.8%were men; their average age was 63.1 years. The 6-sample FOBT and the single digital FOBT had specificities of 93.9%and 97.5%, respectively, as defined by studying 1656 patients with no neoplasia. Sensitivities for detection of advanced neoplasia in 284 patients were 23.9%for the 6-sample FOBT and 4.9%for the digital FOBT. The likelihood ratio for advanced neoplasia was 1.68 (95%CI, 0.96 to 2.94) for positive results on digital FOBT and 0.98 (CI, 0.95 to 1.01) for negative results. Limitations: Most patients were men. Conclusions: Single digital FOBT is a poor screening method for colorectal neoplasia and cannot be recommended as the only test. When digital FOBT is performed as part of a primary care physical examination, negative results do not decrease the odds of advanced neoplasia. Persons with these results should be offered at-home 6-sample FOBT or another type of screening test. Background: Many expert panels recommend colorectal cancer screening for average-risk asymptomatic adults older than 50 years of age. Recent studies have found that 24% to 64% of primary care providers use only the digital fecal occult blood test (FOBT) as their primary screening test. The effectiveness of a single digital FOBT is unknown. Objective: To compare the sensitivity and specificity of digital FOBT and the recommended 6-sample at-home FOBT for advanced neoplasia in asymptomatic persons. Design: Prospective cohort study. Veterans Affairs medical centers. Patients: 3121 asymptomatic patients 50 to 75 years of age. Intervention: 2665 patients had 6-sample at-home FOBT and digital FOBT, followed by complete colonoscopy. Measurements: We measured the sensitivity of digital and 6-sample FOBT for advanced neoplasia and the specificity for no neoplasia. We calculated predictive values ​​and survival ratios for advanced neoplasia, defined as tubular adenomas 10 mm or gr eater, adenomas with villous histology or high-grade dysplasia, or invasive cancer. Results: Of all participants, 96.8% of men; their average age was 63.1 years. The 6-sample FOBT and the single digital FOBT had specificities of 93.9% and 97.5%, respectively, as defined by studying 1656 patients with no neoplasia. Sensitivities for detection of advanced neoplasia in 284 patients were 23.9% for the 6-sample FOBT and 4.9% for the digital FOBT. The likelihood ratio for advanced neoplasia was 1.68 ( 95% CI, 0.96 to 2.94) for positive results on digital FOBT and 0.98 (CI, 0.95 to 1.01) for negative results. Limitations: Most patients were men. Conclusions: Single digital FOBT is a poor screening method for colorectal neoplasia and can not be recommended as the only test. When digital FOBT is performed as part of a primary care physical examination, negative results do not decrease the odds of advanced neoplasia. Persons with these results should be offered at-home 6-sample FOBT or another type of screening test.