Background: Single-balloon enteroscopy (SBE) is a novel, deep-enteroscopy modality for diagnosis and treatment of disorders of the small bowel. Objective: The aim of the study was to examine the performance, yield, and safety of SBE in the initial experience at a tertiary-care center. Design: Retrospective analysis of all SBEs during a 10-month period in 2008. Data were extracted from electronic clinical and endoscopy records. Setting: U.S. tertiary-care center. Patients: All patients referred to our center for SBE during the study period were included in the current analysis. Intervention: SBE. Main Outcome Measurements: Anterograde SBE procedure time, diagnostic yield, and complications. Results: Thirty-eight anterograde SBEs were performed. The mean patient age was 62 years (42% female). Patients were referred for GI bleeding (97%), Crohn's disease, suspected polyps or neoplasia, and abnormal capsule endoscopy results. The mean (± SD) procedure time was 49 ± 19 minutes. The estimated depth of insertion was proximal jejunum (34%), mid-jejunum (45%), and distal jejunum (21%). The SBE diagnostic yield was 47%, with significant findings in 18 patients. Findings included angiectasias, bleeding, abnormal mucosa, ulceration, polyps, and a foreign body. The therapeutic yield was 42%, with lesion ablation performed in 24% of cases. Diagnostic biopsies were performed in 24% of cases and tattooing in 52%. There were no significant complications. Limitations: Single-center, retrospective study. Conclusion: Single-balloon enteroscopy appears to be a safe and efficient method for examination of the mid-small bowel. The significant therapeutic yield (42%) suggests that comparative studies with double-balloon and spiral enteroscopy are warranted. Copyright © 2010 by the American Society for Gastrointestinal Endoscopy.