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Introduction: In the United States, gonadectomy is common and widely promoted as a component of responsible pet ownership. The recent publication of several studies examining the effect of gonadectomy on future health has challenged long-held assumptions and recommendations for gonadectomy in companion animals. The purpose of this study was to characterize the associations between gonadectomy and two outcomes: overweight/obesity and orthopedic injuries, in a large prospective study of Golden Retrievers. Methods: Age at gonadectomy was divided into four categories: intact (reference), ≤ 6 months, > 6 months ‒ ≤ 12 months, and > 12 months. Dogs with a Purina Body Condition Score of 7 or greater were classified as overweight or obese. Orthopedic injuries considered were the first instance of veterinary-reported cranial cruciate ligament injury and clinically evident osteoarthritis. We performed survival analyses on a cohort of Golden Retrievers to estimate the associations of interest using proportional hazards. We adjusted for age at study enrollment, owner-reported activity level, and dog’s sex. Results: Compared to intact dogs, all gonadectomy age categories showed increased risk for the development of overweight/obesity. (≤ 6 months, HR: 1.81, 95% CI: 1.36–2.40), p-value: <0.0001; 6 months to ≤ 12 months, HR: 2.21, 95% CI: 1.77–2.73, p-value: < 0.0001; > 12 months, HR: 1.56, 95% CI: 1.24–1.96, p-value: 0.0001). Compared to intact dogs, dogs who were ≤ 6 months at gonadectomy had increased risk for orthopedic injury (HR: 4.06, 95% CI: 2.15–7.67, p-value: <0.00001). Discussion: This study presents prospectively acquired data demonstrating that gonadectomy is a risk factor for both overweight/obesity and chronic non-traumatic orthopedic injuries in a prospective cohort of Golden Retrievers. Our data suggest that gonadectomy at any age is a risk factor for overweight or obesity, but delaying gonadectomy until dogs are at least 6–12 months of age may help to decrease the risk for orthopedic injury. [ABSTRACT FROM AUTHOR]