OBJECTIVE: To estimate the risks of anaesthetic and sedation-related mortality in companion animals in the UK. (The Confidential Enquiry into Perioperative Small Animal Fatalities, CEPSAF). STUDY DESIGN: A prospective cohort study with nested case-control study. ANIMAL POPULATION: All small animals anaesthetized and sedated at participating centres between June 2002 and June 2004. METHODS: Patient outcomes at 48 hours (alive, dead and killed) were recorded. Anaesthetic and sedation-related death was defined as death where surgical or pre-existing medical causes did not solely cause death. Species-specific risks of anaesthetic-related death and 95% confidence intervals (95% CI) were calculated. Risks were also estimated in the sub-sets of dogs, cats and rabbits that were either healthy or sick (ASA 1-2 and 3-5, respectively). RESULTS: One hundred and seventeen veterinary practices participated in the study and 98 036 dogs, 79 178 cats and 8209 rabbits were anaesthetized and sedated. Overall risks of anaesthetic and sedation-related death in dogs were 0.17% (1 in 601, 95% CI 0.14-0.19%), in cats 0.24% (1 in 419, 95% CI 0.20-0.27%) and in rabbits 1.39% (1 in 72, 95% CI 1.14-1.64%) within 48 hours of the procedure. In healthy dogs, cats and rabbits, the risks were estimated to be 0.05% (1 in 1849, 95% CI 0.04-0.07%), 0.11%, (1 in 895, 95% CI 0.09-0.14%) and 0.73% (1 in 137, 95% CI 0.54-0.93%), respectively. In sick dogs, cats and rabbits, the risks were 1.33%, (1 in 75, 95% CI 1.07-1.60%), 1.40% (1 in 71, 95% CI 1.12-1.68%) and 7.37% (1 in 14, 95% CI 5.20-9.54%), respectively. Postoperative deaths accounted for 47% of deaths in dogs, 61% in cats and 64% in rabbits. Most other small animal species had higher mortality risks. CONCLUSIONS AND CLINICAL RELEVANCE: Small animal anaesthesia appears to be increasingly safe. Greater patient care in the postoperative period could reduce fatalities.