The positions of the pulmonary artery and the aorta are reversed. The aorta is connected to the right ventricle, so most of the blood returning to the heart from the body is pumped back out without first going to the lungs. The pulmonary artery is connected to the left ventricle, so that most of the blood returning from the lungs goes back to the lungs again.

Infants born with transposition survive only if they have one or more connections that let oxygen-rich blood reach the body. One such connection may be a hole between the two atria, called atrial septal defect, or between the two ventricles, called ventricular septal defect. Another may be a vessel connecting the pulmonary artery with the aorta, called patent ductus arteriosus. Most babies with transposition of the great arteries are extremely blue (cyanotic) soon after birth because these connections are inadequate.

To improve the body's oxygen supply, a special procedure called balloon atrial septostomy is used. Two general types of surgery may be used to help fix the transposition. One is a venous switch or intra-atrial baffle procedure that creates a tunnel inside the atria. Another is an arterial switch. After surgery, the long-term outlook is varies quite a bit. It depends largely on how severe the defects were before surgery. Lifelong follow-up is needed.

People with transposition of the great arteries, before and after treatment, are at risk for getting an infection on the heart's walls or valves (endocarditis). To help prevent this, they'll need to take antibiotics before certain dental and surgical procedures.