Background: Retrograde double-balloon enteroscopy (rDBE) is technically a different procedure from its ante-grade counterpart. Its unique indications, success rate, and learning curve have not been specifically reported. Objective: To examine technical issues specific to the rDBE approach. Design: Retrospective review. Setting: Single tertiary-care center. Patients: All patients referred for rDBE. Main Outcome Measurements: Procedure duration, technical success, learning curve, and complications related to rDBE. Results: A total of 59 rDBEs were performed on 56 patients for obscure GI bleeding (46.4%), metastatic carcinoids (23.2%), Crohn's disease (14.3%), and other indications. rDBE enabled a diagnosis in 47.5% of procedures and had a 38% diagnostic rate in finding primary small-bowel lesions that were responsible for metastatic carcinoids. The mean (standard deviation) total procedure time was 111.3 +/- 39.9 minutes. Procedure failure occurred in 12 cases (21%), which is significantly more than reported with antegrade procedures (2%). Failure was more common among patients with a prior abdominal or pelvic surgery (P = .001), and the time to achieve a stable ileal intubation was prolonged in these patients (13.9 vs 38.1 minutes; P = .0006). A trend was noted toward successful small-bowel access and increased lengths of small bowel examined after 20 procedures were performed. Limitations: Small retrospective study. Conclusions: rDBE is effective for the evaluation and the treatment of lower small-intestinal lesions; however, maintaining access through the ileocecal valve may be difficult. Prior surgery may be an important factor associated with failure. A minimum of 20 rDBE procedures was needed to minimize procedure failure, examine a substantial segment of the small-bowel, and shorten procedure duration.