OBJECTIVES: TC-325 is a novel endoscopic hemostatic powder, recently adapted for gastrointestinal (GI) bleeding. However, data on its use, effectiveness, safety, and indications are very limited. To describe a single-centre experience with TC-325 use in a variety of pathologies from the upper and lower GI tract focusing on hemostasis, residency time of the powder on the lesion, and safety.  METHODS: Retrospective chart review of all patients identified through a dedicated endoscopic database as having received TC-325 therapy between July 2011 and July 2013. Primary endpoints include initial hemostasis and early rebleeding (≤ 72 hours). Data on residency time of the product, delayed rebleeding, transfusion and intensive care requirements, need for angioembolization, radiation therapy, and emergent surgery, routine second-look endoscopy and complications associated with TC-325 were also recorded. RESULTS: Overall there were 67 treatments using TC-325 in 60 patients.  Their mean age was 68.1 years ± 13.5, with a male predominance of 65%. There were 21 treatments for non-malignant non variceal upper GI bleeding, 19 for malignant upper GI bleeding, 11 for lower, and 16 for intra-procedural bleeding/prophylaxis therapy. Initial hemostasis was achieved in 66 cases (98.5%), with 6 cases (9.5%) of early rebleeding and 9 cases (14.3%) of delayed rebleeding. No serious adverse events were noted.  Remnants of TC-325 powder were not identified even when second-look endoscopy was performed within 24 hours. CONCLUSIONS: To our knowledge this is the largest retrospective observational study looking at TC-325 in variety of pathologies in the upper and lower GI tract.  Initial hemostasis was excellent; subsequent rebleeding rates varied according to etiology and appearance of lesions. The residency time of the powder was short-lived with complete elimination from the GI tract within 24 hours of use based on a few observations. No serious adverse events were noted.