Background/Aims: There are few reports focusing on therapeutic small bowel endoscopy. The aim of this study was to analyze the results of therapeutic small bowel endoscopy in a large cohort of patients. Methods: A retrospective study of a prospectively collected database comprising all patients undergoing diagnostic and therapeutic small bowel endoscopy in three centers. Results: A total of 614 double-balloon enteroscopies were performed in 534 patients. The most common pathological findings were angiodysplasias and vascular lesions (n = 98, 18%), mucosal ulcers and erosions (n = 95, 17.8%), polyps and tumors (including patients with familiar polyposis syndrome such as Peutz-Jeghers syndrome, familiar adenomatous polyps syndrome, neurofibromatosis, adenocarcinoma, neuroendocrine tumors and gastrointestinal stromal tumors) (n = 52, 9.7%), and strictures (Crohn’s disease, ischemia, tumors) (n = 12, 2.2%). The mean duration of therapeutic small bowel enteroscopy was 67 min (range 30–115) compared to 50 min (range 25–105) for diagnostic procedures (p < 0.05). A therapeutic small bowel endoscopy was performed in 121 patients (22%). Therapeutic procedures included argon plasma coagulation of vascular lesions (n = 73), polypectomy (n = 49), mucosectomy (n = 5), stricture dilation (n = 7), foreign body extraction (n = 7), injection of fibrin glue (n = 10), and clip placement (n = 5). There were a total of 5 complications (0.9%; paralytic ileus, n = 2, pancreatitis, n = 1, bleeding n = 2). No perforations or deaths occurred. Conclusion: Endoscopists performing double-balloon enteroscopy should be trained and prepared to provide therapeutic interventions for small bowel disorders including argon plasma coagulation, injection, hemoclipping, polypectomy, mucosectomy and foreign body extraction. Therapeutic small bowel endoscopy, albeit associated with complications in about 1% of cases, can be considered a relatively safe procedure.