The pathologic anatomic features and associated cardiovascular anomalies of 9 patients with anomalous origin of 1 pulmonary artery (PA) from the ascending aorta seen at the University of Florida and 99 previously reported cases were analyzed. Anomalous origin of the right PA was much more common than anomalous origin of the left PA. The anomalous right PA usually arose from the posterior aspect of the ascending aorta close to the aortic valve. Less commonly, it originated from the lateral ascending aorta just proximal to the innominate artery. Patent ductus arteriosus and aorticopulmonary septal defect were commonly associated with anomalous origin of the right PA; other cardiovascular anomalies were rare. In contrast, tetralogy of Fallot and aortic arch anomalies, e.g., right aortic arch and anomalous origin of the subclavian artery, were common in anomalous origin of the left PA. An association with DiGeorge syndrome, frequently noted with persistent truncus arteriosus, was not seen with anomalous origin of a PA from the ascending aorta. The observations indicate that anomalous origin of the right PA and anomalous origin of the left PA are pathogenetically unrelated to each other and both are unrelated to persistent truncus arteriosus. Moreover, anomalous origin of the right PA arising close to the innominate artery is thought to be pathogenetically distinct from the type that arises close to the aortic valve. These pathogenetic relations should be considered in epidemiologic studies of congenital heart disease.