Background: Colonoscopy may fail to detect neoplasia located on the proximal sides of haustral folds and flexures. The Third Eye Retroscope (TER) provides a simultaneous retrograde view that complements the forward view of a standard colonoscope. Objective: To evaluate the added benefit for polyp detection during colonoscopy of a retrograde-viewing device. Design: Open-label, prospective, multicenter study evaluating colonoscopy by using a TER in combination with a standard colonoscope. Setting: Eight U.S. sites, including university medical centers, ambulatory surgery centers, a community hospital, and a physician's office. Patients: A total of 249 patients (age range 55-80 years) presenting for screening or surveillance colonoscopy. Interventions: After cecal intubation, the disposable TER was inserted through the instrument channel of the colonoscope. During withdrawal, the forward and retrograde video images were observed simultaneously on a wide-screen monitor. Main Outcome Measurements: The number and sizes of lesions (adenomas and all polyps) detected with the standard colonoscope and the number and sizes of lesions found only because they were first detected with the TER. Results: In the 249 subjects, 257 polyps (including 136 adenomas) were identified with the colonoscope alone. The TER allowed detection of 34 additional polyps (a 13.2% increase; P < .0001) including 15 additional adenomas (an 11.0% increase; P < .0001). For lesions 6 mm or larger, the additional detection rates with the TER for all polyps and for adenomas were 18.2% and 25.0%, respectively. For lesions 10 mm or larger, the additional detection rates with the TER for all polyps and for adenomas were 30.8% and 33.3%, respectively. In 28 (11.2%) individuals, at least 1 additional polyp was found with the TER. In 8 (3.2%) patients, the polyp detected with the TER was the only one found. Every polyp that was detected with the TER was subsequently located with the colonoscope and removed. For all polyps and for adenomas, the additional detection rates for the TER were 9.7%/4.1% in the left colon (the splenic flexure to the rectum) and 16.5%/14.9% in the right colon (the cecum to the transverse colon), respectively. Limitations: There was no randomization or comparison with a separate control group. Conclusions: A retrograde-viewing device revealed areas that were hidden from the forward-viewing colonoscope and allowed detection of 13.2% additional polyps, including 11.0% additional adenomas. Additional detection rates with the TER for adenomas 6 mm or larger and 10 mm or larger were 25.0% and 33.3%, respectively. (Clinical trial registration number: NCT00657371.).