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Euthanasia is a complex topic, with animal owners using multiple factors to shape their decision-making process. Previous epidemiological studies have described causes of equine mortality in specific populations, but there is limited evidence regarding factors contributing specifically to equine euthanasia in Great Britain (GB).\ud \ud This observational study used a prospective cohort design: the objectives were to describe owner-reported reasons for euthanasia, estimate the rate of euthanasia and identify associated factors in horses/ponies enrolled in a web-based epidemiological study of laminitis in GB.\ud \ud Self-selected horse/pony owners submitted regular management and health data over 29 months and reported dates and reasons for euthanasia during this period. The overall incidence of euthanasia was estimated and associated factors were identified using multivariable Cox regression modelling, adjusted for age, with variables retained in the final model if P ≤ 0.05.\ud \ud Data were available for 1,070 horses/ponies contributing 1,093 horse-years at risk (HYAR), with 80 owner-reported euthanasias. The incidence of euthanasia was 7.3 euthanasias per 100 HYAR (95% confidence interval [CI] 5.9, 9.1). The most frequently reported health reasons contributing to euthanasia were laminitis-related consequences (25.0%; CI 16.8, 35.5%), colic (21.3%; CI 13.7, 31.4%), non-laminitic lameness (20.0%; CI 12.7, 30.1%) and age-related deterioration, including owner-perceived compromised quality of life (20.0%; CI 12.7, 30.1%). Health-related factors associated with significantly higher rates of euthanasia were colic (hazard ratio [HR] 26.4; CI 12.5, 55.8), pituitary pars intermedia dysfunction (HR 3.0; CI 1.7, 5.4) and lameness due to navicular syndrome (HR 5.9; CI 1.8, 20.0), soft tissue injury (HR 6.5; CI 2.7, 15.6) or laminitis (HR 2.7; CI 1.3, 5.7). Further factors included being pure bred (HR 1.7; CI 1.0, 2.8), female (HR 1.7; CI 1.0, 2.9), having poor owner-perceived hoof quality (HR 2.4; CI 1.1, 5.2), being entirely stabled (HR 5.0; HR 2.1, 12.0), being on loan or under temporary care of the study participant (HR 2.3; CI 1.2, 4.4) and participating in affiliated or professional competitions (HR 5.9; CI 2.4, 14.8). Euthanasia rates were significantly higher in the first two study years compared to the third (P |