The aim of this article is to provide a detailed description of the Golden Retriever Lifetime Study (GRLS), a prospective cohort study investigating nutritional, environmental, lifestyle, and genetic risk factors for cancer and other common diseases in dogs. Primary outcomes of interest include hemangiosarcoma, lymphoma, osteosarcoma, and high-grade mast cell tumors. Secondary outcomes of interest include other cancers, hypothyroidism, epilepsy, atopy, otitis externa, hip dysplasia, heart failure, and renal failure. A total of 3,044 United States Golden Retrievers aged 6 months to 2 years completed baseline enrollment from June 2012 to April 2015. As of May 31, 2021, 2,251 dogs remain engaged in the study, 352 have died, and 441 are lost to follow-up. Extensive annual questionnaires completed by owners and veterinarians gather information about lifestyle, environmental exposures, physical activity, reproductive history, behavior, diet, medications, and diagnoses. Dogs also have annual veterinary examinations and biospecimen collection (blood, serum, hair, nails, feces, urine) for biobanking. Additional reporting, including histology and tumor biobanking, is conducted for any malignancies or deaths. When an animal dies, full medical records are obtained, and necropsies are requested at owner discretion. Full or partial necropsies have been performed on 218 dogs. Questionnaire data are freely available to researchers with approved credentials who agree to a data use agreement. In addition, researchers can submit proposals to utilize biospecimens or obtain additional data.