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To assess the safety and efficacy of the Instinct clip in the acute endoscopic treatment of upper gastrointestinal bleeding (UGIB).This is the first large series reporting this clip in achieving hemostasis. A retrospective descriptive chart review was performed on patients presenting with recent overt GI bleeding treated with endoclip therapy at Mount Sinai Beth Israel Medical Center between May 2013 and January 2016. Results are expressed in absolute numbers, percentages, and trends.In total, 178 consecutive patients with UGIB were included. Source of bleeding was identified as duodenal ulcer (29.2%), gastric ulcer (22.5%), gastro-esophageal junction tear (8.4%), anastomosis (5.6%), erosive gastropathy (5.6%), Dieulafoy (5.1%), gastric polyp (4.5%), postendoscopic procedure (3.9%), angioectasia (3.4%), esophageal ulcer (2.8%), benign duodenal mass (2.8%), peg tube site (2.3%), gastric neoplasm (1.7%), esophagitis (1.1%), and small bowel ulcer (1.1%). Lesions demonstrated active bleeding in 47.5% (11.3% spurting and 36.2% oozing) and nonbleeding lesions in 52.5% (25.0% visible vessel, 11.9% hematin in ulcer base, 10.0% adherent clot, 5.6% flat spot). Initial hemostasis was achieved in 96.6%. Additional methods were used in 24.1% (argon plasma coagulation and epinephrine injection in 21.3%, surgery in 0.6%, and interventional radiology in 2.2%). There were no adverse events. In-hospital rebleeding was 7.3% and 3.9% presented with rebleeding within 30 days. Average procedure duration was 22.9 minutes and average length of hospital stay was 11.3 days.The Instinct clip, when used for UGIB, seems to be safe and effective with similar rebleeding rates compared with other modalities.