Abstract Objective—To determine clinical features of dilated cardiomyopathy (DCM) in Great Danes and to determine whether DCM is familial in this breed. Design—Retrospective study. Animals—17 Great Danes with DCM. Procedure—Medical records of Great Danes in which DCM was diagnosed on the basis of results of echocardiography (fractional shortening < 25%, endsystolic volume index > 30 ml/m² of body surface area) were reviewed. Pedigrees were obtained for affected animals, as well as for other Great Danes in which DCM had been diagnosed. Results—Dilated cardiomyopathy appeared to be familial and was characterized by ventricular dilatation, congestive heart failure (left-sided or biventricular), and atrial fibrillation. Pedigree analysis suggested that DCM was inherited as an X-linked recessive trait, but the mode of inheritance could not be definitively identified. Conclusions and Clinical Relevance—Results suggest that DCM may be an X-linked recessive trait in Great Danes. Thus, dogs with DCM probably should not be used for breeding, and female offspring of affected dogs should be used cautiously. Male offspring of affected females are at an increased risk of developing DCM and should be evaluated periodically for early signs of disease. Results of pedigree analysis were preliminary and should be used only as a guide for counseling breeders, rather than as a basis for making breeding decisions. (J Am Vet Med Assoc 2001;218:729–732)