BACKGROUND: Histoacryl glue (N-butyl-2-cyanoacrylate) has well-established utility in the endoscopic management of gastrointestinal variceal bleeding. The role of Histoacryl glue in non-variceal bleeding is less clear, and there are few articles describing its use in this setting. METHODS: Six patients with intractable non-variceal gastrointestinal bleeding were managed using injection of Histoacryl glue. All patients had previously failed conventional endostasis and/or interventional angioembolization and were not suitable for emergency salvage surgery due to serious comorbidities or unacceptable anaesthetic risk. An endoscopic Lipiodol-Histoacryl-Lipiodol sandwich injection technique was used in these patients. The clinical outcomes and complications were evaluated. RESULTS: There were four females and two males with a mean age of 55 years. Bleeding lesions included gastric ulcers (n = 2), duodenal ulcers (n = 2), duodenal gastrointestinal stromal tumor (GIST) (n = 1) and rectal ulcers (n = 1). All patients had successful Histoacryl endostasis without the requirement for salvage surgery. There was no treatment-related morbidity and no mortality. Two patients had further bleeding after initial Histoacryl endostasis, which was successfully controlled with further endoscopic Histoacryl injection. CONCLUSION: Histoacryl endostasis should be included in the treatment algorithm for refractory non-variceal gastrointestinal bleeding.