BACKGROUND: Patients with Trisomy 21 are now living well into adulthood. Little data exists to assist the cardiologist in the care of these patients. We sought to examine the cardiac and general health status of adults with Trisomy 21 undergoing cardiac evaluation. METHODS & RESULTS: A retrospective review of all affected adults >21years followed at 2 tertiary care institutions was performed. Of 193 patients identified, median age was 31 (range 21.1-60.5) years. Cardiac surgery was performed in childhood in 127 with 30 patients who did not undergo surgery developing Eisenmenger syndrome. The remaining 36 patients did not warrant early surgical intervention. Six patients were lost to follow-up. Significant cardiac residua were present in 117 (62%). Arrhythmias were present in 53 (28%) with 15 having atrial fibrillation (8%). Non-cardiac comorbidities were common and included sleep apnea, pulmonary hypertension, thyroid dysfunction, thromboses and recurrent infections. Hospitalization in adulthood occurred in 58 patients (51%); pneumonia and cardiac related surgeries being the most common reasons for hospitalization. Average age of death (n=23) was 39.8+/-8.5years. Transition of care to an adult provider was uncommon occurring in 54 (27%) patients. On multivariate analysis, presence of younger age and absence of pulmonary hypertension were the sole predictors of survival for the group as a whole, as well as those patients without Eisenmenger syndrome. CONCLUSIONS: Adults with Trisomy 21 have frequent cardiac and non-cardiac co-morbidities. Cardiologists caring for these patients should be familiar with the adult acquired medical problems these patients encounter.