BACKGROUND Single-balloon endoscopy (SBE) has been introduced as a simplified endoscopy technique after the promotion of double-balloon endoscopy (DBE). The difference in clinical performance between DBE and SBE is still not very clear. In this study, we aimed to compare the efficacy and safety between these 2 endoscopic procedures. MATERIAL AND METHODS A total of 173 patients with suspected small bowel disease were enrolled into this study from January 2007 to December 2011. All cases were divided into DBE or SBE groups according to the endoscopic procedures they underwent. We then compared the diagnostic yield, the influence of DBE and SBE on the diagnostic/therapeutic course, the examination time, and post-procedure discomfort between DBE and SBE groups. RESULTS We observed no notable adverse events during or after the examinations. Additionally, SBE displays a significantly higher diagnostic rate (62.0%) than DBE (35.6%) via the anal approach (P=0.0137), while there was no difference in positive diagnostic rate between DBE and SBE via the oral route. Remarkably, it takes significantly less time to perform SBE examinations (38.86±5.64 minutes) than DBE procedures (41.80±6.50 minutes) via the oral route (P=0.048), although the average examination time for DBE is close to that for SBE via the anal route (P=0.952). However, DBE and SBE are similar in terms of their impact on the diagnostic/therapeutic course and complication rate. CONCLUSIONS Both SBE and DBE are very safe procedures to perform and SBE is a preferred choice for the evaluation of small bowel diseases in terms of diagnostic rate via the anal route compared with DBE.