IntroductionData on the safety and efficacy of double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE) are conflicting. We aimed to compare the efficacy and safety of retrograde DBE to SBE. MethodsWe performed a retrospective analysis of all patients who underwent retrograde DBE or SBE at a large tertiary referral center from 2008 to December 2018. Outcomes assessed included technical success, diagnostic yield, therapeutics, depth of insertion, and procedural duration. ResultsA total of 523 (403 DBE, 120 SBE) patients underwent retrograde enteroscopy during the study period. The mean age was 59.4 +/- 17.24 and 59.57 +/- 16.94 years in DBE and SBE groups, respectively. There was no difference in technical success (91.0% vs. 92.5%, P = 0.85), diagnostic yield (40.9% vs. 40.8%, P = 0.95), and therapeutics (17.1% vs. 19.1%, P = 0.61) between DBE and SBE. Compared to SBE, DBE had significantly shorter mean procedure time (26.5 +/- 34.5 min vs. 34.8 +/- 29.4 min, P = 0.01) and higher maximal depth of insertion from ileocecal valve (108.1 +/- 84.1 cm vs. 73.3 +/- 63.4 cm, P = 0.001). Safety events were rare and similar in both groups. ConclusionRetrograde DBE is associated with a significantly higher depth of insertion and shorter procedural duration, but similar diagnostic yield and technical success compared to SBE.