BACKGROUND AND STUDY AIM: The novel over-the-scope clip (OTSC) allows for excellent apposition of tissue, potentially permitting hemostasis to be achieved in various types of gastrointestinal lesions. This study aimed to evaluate the usefulness and safety of OTSCs for endoscopic hemostasis in patients with upper gastrointestinal bleeding in whom traditional endoscopic methods had failed. PATIENTS AND METHODS: A retrospective case series of all patients who underwent placement of an OTSC for severe recurrent upper gastrointestinal bleeding over a 14-month period was studied. Outcome data for the procedure included achievement of primary hemostasis, episodes of recurrent bleeding, and complications. RESULTS: Twelve consecutive patients (67 % men; mean age 59, range 29 - 86) with ongoing upper gastrointestinal bleeding despite previous endoscopic management were included. They had a mean ASA score of 3 (range 2 - 4), a mean hemoglobin of 7.2 g/dL (range 5.2 - 9.1), and shock was present in 75 % of patients. They had all received packed red blood cells (mean 5.1 units, range 2 - 12). The etiology of bleeding was: duodenal ulcer (n = 6), gastric ulcer (n = 2) Dieulafoy lesion (n = 2), anastomotic ulceration (n = 1), Mallory - Weiss tear (n = 1). Hemostasis was achieved in all patients. Rebleeding occurred in two patients 1 day and 7 days after OTSC placement. There were no complications associated with OTSC application. CONCLUSIONS: OTSC use represents an effective, easily performed, and safe endoscopic therapy for various causes of severe acute gastrointestinal bleeding when conventional endoscopic techniques have failed. This therapy should be added to the armamentarium of therapeutic endoscopists.