Background: Patient safety is essential in small animal anaesthesia. This study aimed to assess anaesthesia-related deaths in cats worldwide, identify risk and protective factors and provide insights for clinical practice., Methods: A prospective multicentre cohort study of 14,962 cats from 198 veterinary centres across different countries was conducted. Data on anaesthesia-related deaths, from premedication up to 48 hours postextubation, were collected. Logistic regression was used to analyse patient demographics, American Society of Anesthesiologists (ASA) classification, procedure type and anaesthetic drugs., Results: The anaesthesia-related mortality was 0.63%, with 74.5% of deaths occurring postoperatively. Cats with cachexia, a higher ASA status or who underwent abdominal, orthopaedic/neurosurgical or thoracic procedures exhibited elevated mortality. Mechanical ventilation use was associated with increased mortality. Mortality odds were reduced by the use of alpha 2 -agonist sedatives, pure opioids in premedication and locoregional techniques., Limitations: Limitations include non-randomised sampling, potential biases, unquantified response rates, subjective death cause classification and limited variable analysis., Conclusions: Anaesthetic mortality in cats is significant, predominantly postoperative. Risk factors include cachexia, higher ASA status, specific procedures and mechanical ventilation. Protective factors include alpha 2 -agonist sedatives, pure opioids and locoregional techniques. These findings can help improve anaesthesia safety and outcomes. However, further research is required to improve protocols, enhance data quality and minimise risks., (© 2024 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)