Two half-sibling neonatal llamas (Lama glama) and one unrelated adult llama were presented with various complaints, including failure to thrive, respiratory distress, and excessive recumbency. The related camelids were born in successive years to the same dam but from unrelated sires. Thoracic auscultation revealed significant systolic and diastolic murmurs on both sides of the chest in all three llamas, and arterial blood gas evaluation revealed hypoxemia in two llamas. Echocardiographic examinations revealed large atrioventricular septal (AVS) defects in all three llamas. Two llamas were euthanized after diagnosis and the third died 4 mo later. Postmortem examination confirmed large AVS defects in all animals. There also was marked cardiomegaly in each animal. The discovery of such a cardiac anomaly in these three camelids suggests that it may be common in this species and may have a genetic basis.