BackgroundAlthough regular health screening is recommended, long‐term follow‐up data in healthy aged cats are lacking.ObjectivesDetermine the most common conditions in a large group of apparently healthy older cats and which diseases are manifested within 2 years in cats confirmed to be healthy based on extensive health screening.AnimalsClient‐owned cats.MethodsProspective study. Thorough history, physical examination, blood tests, and urinalysis were performed in 259 apparently healthy mature adult (7‐10 years) and senior (>10 years) cats. Semi‐annual follow‐up examinations were performed in 201 confirmed healthy cats.ResultsAt baseline, 21% of apparently healthy cats were not considered healthy but were diagnosed with International Renal Interest Society (IRIS) ≥ stage 2 chronic kidney disease (CKD; 7.7%) or hyperthyroidism (4.6%), among other disorders. Disease occurred significantly more frequently in senior cats compared with mature adult cats. In addition, 40% cats were overweight, 35% had moderate to severe dental disease, and 22% had abnormal cardiac auscultation findings. Within 2 years, 28% of mature adult and 54% of senior cats that were confirmed healthy at inclusion developed new diseases, most commonly IRIS ≥ stage 2 CKD (cumulative incidence, 13.4%), hyperthyroidism (8.5%), chronic enteropathy, hepatopathy or pancreatitis (7.5%), or neoplasia (7%).Conclusions and Clinical ImportanceThe high prevalence and 2‐year incidence of physical examination abnormalities and systemic diseases in apparently healthy older cats argue for regular health screening in cats ≥7 years of age. Although more common in senior cats, occult disease also occurs in mature adult cats, and owners should be informed accordingly.