In single-ventricle patients with native-to-neoaortic anastomoses, the native aortic root serves as a conduit to the coronary arteries. Thrombosis of the native aortic root has been described only in small, limited reports. We described our center’s experience with this rare adverse event. All single-ventricle patients who underwent native-to-neoaortic anastomosis from 2002 to 2017 were compiled from institutional databases. Chart review identified cases of native aortic root thrombosis. Of 467 patients, there were 9 (2%) cases of native aortic root thrombosis; all had hypoplastic left heart syndrome. Timing of thrombosis varied and occurred following each stage of single-ventricle palliation. For treatment, 8 patients received systemic anticoagulation and one patient did not receive any treatment. One patient also underwent percutaneous thrombectomy. Three patients (33.3%) died during the follow-up period. Among survivors, 4/6 had right ventricular systolic function that was mildly depressed or worse at a median follow-up of 8.3 years (interquartile range 1.3–10.8). Native aortic root thrombosis is a rare complication occurring at various stages of single-ventricle palliation. In this series, 6 of 9 patients (66.6%) survived; however, ventricular function was often compromised. No risk factors were identified to focus preventative therapies.