Background/Aims: Video capsule endoscopy (CE) can provide a negative result despite the presence of clinically significant small-bowel lesions. We therefore performed a prospective study to elucidate whether repeated back-to-back CE increases the diagnostic yield over a single CE in patients with obscure gastrointestinal bleeding (OGIB). Methods: Sixteen patients with OGIB were prospectively enrolled and underwent back-to-back CE investigation with a 24-hour interval. All CE videos were interpreted by two experienced readers at a maximum 15 frames/second in a random order. Results: The diagnostic yield of the single CE was 37.5% for the first CE, 43.8% for the second CE, and 62.5% for the back-to-back CE. The overall mean lesion-detection rates of the first and second CEs were 42.2% and 64.6%, respectively. The bowel preparation status of the second CE was improved in 37.5% and unchanged in 62.5% of cases as compared with that of the first CE. Conclusions: These results indicate that back-to-back CE may increase the diagnostic yield and lesion-detection rate over a single CE in patients with OGIB. Therefore, if the first CE is not diagnostic in a patient with OGIB, repeat back-to-back CE may be considered as a candidate for further workup. (Gut Liver 2010;4:54-59)