During the development of the heart in the fetus, a common large artery, called a truncus arteriosus, carries blood from the two lower chambers (ventricles) to the body and lungs. This truncus later divides into two separate arteries, the aorta and the pulmonary artery. In addition, the wall between the ventricles grows, completely separating the arteries. When a child is born with truncus arteriosus, these normal steps in development have failed to occur. "Red blood" from the left side of the heart mixes with "blue blood" from the right side of the heart at the opening between the ventricles. This mixed blood is then pumped out of the heart through the truncus arteriosus. From there, some blood gets to the lungs through pulmonary arteries, which branch off from the truncus, and the rest goes to the body by way of the aorta.

Babies with truncus arteriosus may be cyanotic (bluish color of the lips, skin, and nailbeds) because the mixed blood is low in oxygen. They tend to be small, tire easily, and breathe rapidly because their heart works harder than normal. Surgery to repair this defect is required very early in life.

Following surgery, children require penicillin (also called SBE prophylaxis) prior to any dental work or surgery on the mouth, bowel, or bladder. This helps prevent the uncommon, but possible occurrence of bacterial infection affecting the heart near the defect of the heart valves.