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Objective PuraStat is a topical haemostatic agent used for treatment and prevention of bleeding. Our aim was to evaluate the efficacy and safety of using PuraStat during advanced endoscopic resection procedures in a multicentre prospective setting.Design/methods This is a multicentre prospective evaluation on efficacy and safety of PuraStat when used in the treatment of intraprocedural bleeding and prevention of delayed bleeding during the study period from 2019 to 2021. High-risk tissue resections (HRTR) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for large and complex lesions from the oesophagus, stomach, duodenum and colon were included. Data on the type of bleed, haemostatic measures used, and efficacy and safety of PuraStat were prospectively collected. A descriptive analysis was performed and expressed as proportions.Results PuraStat was used in a total of 448 patients with HRTR. PuraStat was used for treatment of intraprocedural bleeding in 105 patients. Overall haemostatic efficacy in this group was 91.43%. All 448 patients had prophylactic application of PuraStat on the resection base to prevent delayed bleeding. The observed overall delayed bleeding rate for the entire cohort was 1.34%. On subgroup analysis, we found that this was highest in the duodenum (8.69%) followed by 1.80% in the right colon (EMR and ESD). There were no delayed bleeds in the oesophagus, stomach and left colon.Conclusions Our data demonstrates that PuraStat is safe and appears to be effective in the treatment of intraprocedural bleeding and prevention of delayed bleeding after high-risk endoscopic resections.Trial registration number NCT03983707.