Double-balloon endoscopy (DBE) has been used in clinical practice for nearly 10 years. To systematically collect and produce pooled data on indications, detection rate, total enteroscopy, complications, and the composition of positive findings in diagnostic DBE. A systematic review. We searched PubMed between January 1, 2001 and March 31, 2010 for original articles about DBE evaluation of small-bowel diseases. Data on total number of procedures, distribution of indications, pooled detection rate, pooled total enteroscopy rate, and composition of positive findings were extracted and/or calculated. In addition, the data involving DBE-associated complications were analyzed. A total of 66 English-language original articles involving 12,823 procedures were included. Suspected mid-GI bleeding (MGIB) was the most common indication (62.5%), followed by symptoms/signs only (7.9%), small-bowel obstruction (5.8%), and Crohn's disease (5.8%). The pooled detection rates were 68.1%, 68.0%, 53.6%, 63.4%, and 85.8% for overall, suspected MGIB, symptoms/signs only, Crohn's disease, and small-bowel obstruction, respectively. Inflammatory lesions (37.6%) and vascular lesions (65.9%) were the most common findings, respectively, in suspected MGIB patients of Eastern and Western countries. The pooled total enteroscopy rate was 44.0% by combined or antegrade-only approach. The pooled minor and major complication rates were 9.1% and 0.72%, respectively. Inclusion and exclusion criteria were loosely defined. The detectability and complication risk of diagnostic DBE are acceptable. Suspected MGIB is the most common indication, with a relatively high detection rate, but there was a difference in its causes between Western and Eastern countries. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.