Background With the introduction of new techniques to image the small bowel, there remains uncertainty about their role for diagnosing Crohn's disease. Objective To assess the sensitivity and specificity of capsule endoscopy (CE), CT enterography (CTE), ileocolonoscopy, and small-bowel follow-through (SBFT) in the diagnosis of small bowel Crohn's disease. Methods Prospective, blinded trial. Setting Inflammatory bowel disease clinic at an academic medical center. Patients Known or suspected Crohn's disease. Exclusion criteria included known abdominal abscess and non-steroidal anti-inflammatory drug (NSAID) use. Partial small-bowel obstruction (PSBO) at CTE excluded patients from subsequent CE. Interventions Patients underwent all 4 tests over a 4-day period. Main Outcome Measurements Sensitivity, specificity, and accuracy of each test to detect active small-bowel Crohn's disease. The criterion standard was a consensus diagnosis based upon clinical presentation and all 4 studies. Results Forty-one CTE examinations were performed. Seven patients (17%) had an asymptomatic PSBO. Forty patients underwent colonoscopy, 38 had SBFT studies, and 28 had CE examinations. Small-bowel Crohn's disease was active in 51%, absent in 42%, inactive in 5%, and suspicious in 2% of patients. The sensitivity of CE for detecting active small-bowel Crohn's disease was 83%, not significantly higher than CTE (83%), ileocolonoscopy (74%), or SBFT (65%). However, the specificity of CE (53%) was significantly lower than the other tests (P < .05). One patient developed a transient PSBO due to CE, but no patients had retained capsules. Limitation Use of a consensus clinical diagnosis as the criterion standard—but this is how Crohn's disease is diagnosed in practice. Conclusions The sensitivity of CE for active small-bowel Crohn's disease was not significantly different from CTE, ileocolonoscopy, or SBFT. However, lower specificity and the need for preceding small-bowel radiography (due to the high frequency of asymptomatic PSBO) may limit the utility of CE as a first-line test for Crohn's disease. With the introduction of new techniques to image the small bowel, there remains uncertainty about their role for diagnosing Crohn's disease. To assess the sensitivity and specificity of capsule endoscopy (CE), CT enterography (CTE), ileocolonoscopy, and small-bowel follow-through (SBFT) in the diagnosis of small bowel Crohn's disease. Prospective, blinded trial. Inflammatory bowel disease clinic at an academic medical center. Known or suspected Crohn's disease. Exclusion criteria included known abdominal abscess and non-steroidal anti-inflammatory drug (NSAID) use. Partial small-bowel obstruction (PSBO) at CTE excluded patients from subsequent CE. Patients underwent all 4 tests over a 4-day period. Sensitivity, specificity, and accuracy of each test to detect active small-bowel Crohn's disease. The criterion standard was a consensus diagnosis based upon clinical presentation and all 4 studies. Forty-one CTE examinations were performed. Seven patients (17%) had an asymptomatic PSBO. Forty patients underwent colonoscopy, 38 had SBFT studies, and 28 had CE examinations. Small-bowel Crohn's disease was active in 51%, absent in 42%, inactive in 5%, and suspicious in 2% of patients. The sensitivity of CE for detecting active small-bowel Crohn's disease was 83%, not significantly higher than CTE (83%), ileocolonoscopy (74%), or SBFT (65%). However, the specificity of CE (53%) was significantly lower than the other tests (P < .05). One patient developed a transient PSBO due to CE, but no patients had retained capsules. Use of a consensus clinical diagnosis as the criterion standard—but this is how Crohn's disease is diagnosed in practice. The sensitivity of CE for active small-bowel Crohn's disease was not significantly different from CTE, ileocolonoscopy, or SBFT. However, lower specificity and the need for preceding small-bowel radiography (due to the high frequency of asymptomatic PSBO) may limit the utility of CE as a first-line test for Crohn's disease.