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Double-balloon enteroscopy (DBE) is now an established method for diagnostic and therapeutic small-bowel endoscopy. Single-balloon enteroscopy (SBE) has been introduced to simplify the technique. A prospective randomized study was carried out to compare the two methods.The study included 100 patients (50 in each group; 63 men, 37 women; mean age 55 years), with no previous small-bowel or colon surgery. The indications for enteroscopy were (suspected) mid-gastrointestinal bleeding, Crohn's disease, small-bowel masses, chronic diarrhea or abdominal pain or both, and other conditions. Fujinon instruments were used, with either two balloons or one. The end point of the study was complete enteroscopy as the most objective parameter.No severe complications such as perforation, bleeding, or pancreatitis occurred. Instrument preparation time was significantly faster with SBE than with DBE (P<0.0001). Complete enteroscopy was achieved with the DBE technique in 66% of cases (33 patients), either with the oral route alone or with combined oral and anal approaches. With the SBE technique, the complete enteroscopy rate was significantly lower at 22% (P<0.0001; 11 patients, only with oral and anal routes combined). The rate of therapeutic consequences for the patients based on diagnostic yield and negative complete enteroscopy was significantly higher (P=0.025) in the DBE group at 72%, compared with 48% in the SBE group.The complete enteroscopy rate was three times higher with DBE than with SBE, accompanied by a higher diagnostic yield. DBE must therefore continue to be regarded as the nonsurgical gold standard procedure for deep small-bowel endoscopy.