Background The performance characteristics of spiral enteroscopy have not been well-described. Objective To determine the technical performance, diagnostic and therapeutic yields, and safety of oral spiral enteroscopy in patients with suspected or established small-bowel pathology. Design Prospective, multicenter, cohort study, with centralized database. Setting Ten U.S. tertiary-care medical centers. Patients This study involved 148 participants, of whom 101 were referred for obscure bleeding. All participants referred for antegrade deep enteroscopy were considered eligible. Intervention Spiral enteroscopy. Main Outcome Measurements Examination duration, depth of insertion, spiral enteroscopy findings, mucosal assessment upon withdrawal, and patient symptom assessment (day 1 and day 7 after the procedure). Results Spiral enteroscopy was successful in 93% of patients, with a median depth of insertion beyond the angle of Treitz of 250 cm (range 10-600 cm). The mean (± standard deviation) total procedure time was 45.0 ± 16.2 minutes for all procedures, and 35.4 minutes for diagnostic procedures. The diagnostic yield was 65%, of which 48% revealed more than one abnormality. The most common findings were angiectasias (61.5%), inflammation (7.5%), and neoplasia (6.8%). Argon plasma coagulation ablation accounted for 64% of therapeutic interventions. Limitations This was not a randomized, controlled trial of deep enteroscopy modalities. Conclusion Spiral enteroscopy appears to be safe and effective for evaluation of the small bowel. The procedure duration, depth of insertion, and diagnostic and therapeutic yields compare favorably with previously published data on other deep enteroscopy techniques such as single-balloon and double-balloon enteroscopy. Comparative studies are warranted. © 2010 American Society for Gastrointestinal Endoscopy.