Background: Single-balloon enteroscopy (SBE) was introduced as an alternative to double-balloon enteroscopy (DBE) for the investigation and management of small-bowel conditions. To date, there is only 1 randomized, controlled trial comparing SBE and DBE in a Western population. Objective: To compare the 2 instruments in a Western population to assess for differences in clinical outcomes and insertion depth (ID). A novel method to determine ID by counting folds on withdrawal was used. Design: Multicenter, randomized, controlled trial. Setting: University hospitals in Melbourne and Sydney, Australia. Patients: Patients with suspected or proven small-bowel disease. Interventions: SBE and DBE. Main Outcome Measurement: The primary endpoint was diagnostic yield (DY). Secondary endpoints were therapeutic yield (TY), procedure times, and ID. An intention-to-treat analysis was performed. Results: A total of 116 patients were screened, and 107 patients were enrolled between July 2008 and June 2010, in whom 119 procedures were undertaken (53 SBEs and 66 DBEs). DY was 57% for SBE and 53% for DBE (P = .697). TY was 32% for SBE and 26% for DBE (P = .490). The median enteroscopy times were identical for SBE and DBE at 60 minutes. The mean ID by the fold-counting method for antegrade procedures was 201.1 folds for SBE and 258.6 folds for DBE (P = .046). After multiple comparisons adjustment, this difference did not reach statistical significance. Mean IDs by using the visual estimation method for SBE and DBE were, respectively, 72.1 cm and 75.2 cm (P = .835) for retrograde procedures and 203.8 cm and 234.1 cm (P = .176) for antegrade procedures. Limitations: Unable to reach target sample size, mostly single-center recruitment, novel method to determine ID, which requires further validation. Conclusions: SBE has DY, TY, and procedure times similar to those of DBE. There were no statistically significant differences in ID between SBE and DBE. By using the fold-counting method for antegrade procedures, the estimated IDs for SBE and DBE were 201.1 folds versus 258.6 folds (P = .046; P = not significant after adjustment for multiple comparisons).