Abstract Background Limited data are available on the clinical impact of single balloon enteroscopy. Aims To evaluate the diagnostic and therapeutic yield of single balloon enteroscopy in patients with suspected small bowel disease. Methods Data on patients with suspected small bowel disease based on non-invasive imaging, who were subjected sequentially to enteroscopy were prospectively collected. Results 131 procedures were performed in 111 patients. The mean procedure time was 61±33min for the oral approach, and 78±41min for the anal approach. The mean insertion depth was 223±93cm beyond the ligament of Treitz, and 96±56 beyond the ileo-cecal valve. A diagnosis suspected with prior small bowel tests was confirmed in 82 patients, confidently excluded in 20, while in 9 the suspected area was not reached. Total enteroscopy was deemed clinically unnecessary in 94 patients; when total enteroscopy was attempted, it was achieved in 8 out 17 patients. Endoscopic therapeutic interventions were performed in 39 patients, medical treatment was started in 30, whereas 18 underwent to surgery. No major complications were registered. Conclusions This study shows that single balloon enteroscopy appears to be an helpful and safe procedure with a high clinical impact, especially when it is placed in decision-making as a third level examination.