This study compared teenaged and adult patients with Down syndrome (DS) who underwent cardiac surgery with those without DS. Patients with DS had longer hospital stays, more mechanical ventilation, higher rates of postoperative complications, and greater need for respiratory support, but no increased mortality. Risk factors for extended hospital stays included pulmonary medication use, immunodeficiency, and moderate or greater tricuspid regurgitation. Despite these challenges, cardiac surgery can be safely performed in older DS patients with careful management of these risk factors.