Background: The occurrence of small vessel arteriosclerosis in the myocardium, kidney, and lung in dogs with naturally occurring myxomatous mitral valve disease has not been previously investigated systematically. Methods: Twenty-one dogs with naturally occurring congestive heart failure and 21 age-matched, sex-matched, and weight-matched control dogs underwent extensive pathological and histopathological examination. Morphometry and scoring of tissue sections were used to measure arterial narrowing and fibrosis in the myocardium, kidney, and lung; and intimal thickness and plaque formation in the aorta and pulmonary artery. Results: Dogs with congestive heart failure had significantly more arterial narrowing in the left ventricle (P<.003), lung (P<.0001), and kidney (p<.02); intimal-medial thickening in the pulmonary artery (P=.04); and fibrosis in the left ventricle (P<.0001) than control dogs. However, they did not have more plaque formation or intimal-medial thickening in the aorta than controls. There was significantly more arterial narrowing in papillary muscles than in all other locations in dogs with congestive heart failure (P<.002). In control dogs, arterial changes were less pronounced and did not differ in different locations. Conclusions: Dogs with naturally occurring myxomatous mitral valve disease have significantly more arterial changes in the myocardium, lung, and kidney, and significantly more fibrosis in the myocardium than control dogs. This could have important implications in the management of myxomatous mitral valve disease and raises interesting questions about the occurrence and importance of intramural small vessel disease in humans with primary mitral valve prolapse.