Double-balloon enteroscopy (DBE) is a new endoscopic tool that not only allows diagnostic workup of small bowel diseases, but also makes it possible to carry out therapeutic interventions. However, for a variety of reasons, endoscopic therapy appears to be more difficult to carry out deep in the small bowel than in the upper or lower gastrointestinal tract. The purpose of this study was to evaluate the acute technical success and acute complication rate of DBE. Between June 2003 and July 2006, 353 patients (152 women, 201 men; mean age 60.3 +/- 17.1 yr) with suspected or known small bowel disease underwent 635 consecutive DBE procedures. The majority of the patients were suffering from midgastrointestinal bleeding (N = 210, 60%). The overall diagnostic yield was 75% (265/353) for relevant lesions in the small bowel. The overall therapeutic yield was 67% (236/353). Endoscopic therapy was performed in 59% of these patients (139/236). All therapeutic interventions were done in an inpatient manner. The majority of the procedures were carried out with the patients under conscious sedation (N = 130, 73%); sedation with propofol was administered in 37 (20.8%) and with a combination of propofol and meperidine in 11 (6.2%) investigations. A total of 178 therapeutic procedures was carried out. A median of 270 cm of the small bowel was visualized using the oral route and a median of 150 cm using the anal route. The investigation time averaged 78 +/- 30 minutes. The endoscopic treatments included argon plasma coagulation (APC, 102 treatment sessions), injection therapy (N = 2), a combination of APC and injection (N = 6), polypectomies (N = 46), dilation therapy (N = 18), and foreign-body extraction (N = 3). In 6/178 cases (3.4%), polypectomy (N = 2), dilation (N = 3), and implantation of a self-expanding metal stent (N = 1) could not be performed successfully for technical or anatomical reasons. Severe treatment-associated complications occurred in six of the 178 therapeutic procedures (3.4%) and 4/139 patients (2.9%), consisting of bleeding (N = 2) and perforation (N = 3) during and after polypectomy of large polyps (>3 cm in size), as well as one case of segmental enteritis after APC. Endoscopic therapeutic interventions can be performed safely even in the more difficult conditions of the small bowel in the majority of patients. Polypectomy of large polyps appears to be the procedure associated with the highest risk.