The "great arteries" in this anomaly refer to the aorta and the pulmonary artery, the two major arteries carrying blood away from the heart.

In cases of transposition of the great arteries, these vessels arise from the wrong ventricle. They are "transposed" from their normal position so that the aorta arises from the right ventricle and the pulmonary artery from the left ventricle.

Other heart defects may occur along with transposition of the great arteries. About 25 percent of children with transposition will also have a ventricular septal defect (VSD) . In nearly a third, the branching pattern of the coronary arteries as they leave the transposed aorta is unusual. Infants may also have narrowing below the pulmonary valve that blocks blood flow from the left ventricle to the lungs.

Transposition creates a situation where the systemic (to the body) and pulmonary (to the lungs) circulations are in parallel rather than in series. This means the oxygen-poor ("blue") blood returning from the body and coursing through the right atrium and right ventricle is pumped out to the aorta and to the body, while the oxygen-rich ("red") blood returning from the lungs and coursing through the left atrium and ventricle is sent back to the lungs via the pulmonary artery.

Unless there is some place in the circulation where the oxygen-rich and oxygen-poor blood can mix, all of the organs of the body will be deprived of necessary oxygen.

Thus, in order to survive prior to surgery, the blood must mix somewhere in the heart. If present, a ventricular septal defect (VSD) will allow some mixing, but often this does not allow enough mixing. Other places that mixing may occur are through an atrial septal defect (ASD) or a patent ductus arteriosus (PDA). Techniques used to improve mixing before surgery are described below.