The duodenum in humans is shaped somewhat like a "C" and is thus divided into three parts.

The first part of the duodenum connects to the stomach at the pylorus.

The second part of the duodenum is where the common bile duct connects to the gastrointestinal tract, at the Ampulla of Vater. Occasionally, the pancreatic duct connects separately to the duodenum from the bile duct but it always joins this part of the duodenum.

The third part of the duodenum connects with the jejunum, which forms the bulk of the small intestine.

The entire duodenum is retroperitoneal. It is intimately related to several structures: on its right, the right kidney; to its left, nestled in the "C" of the duodenum, lies the head of the pancreas; directly posterior lies the common bile duct, the portal vein and inferior vena cava; the celiac trunk originates near the pylorus, where the duodenum begins and the superior mesenteric artery originates in the centre of the C of the duodenum; overlying the duodenum is the hepatic flexure of the colon and part of the transverse colon as well as folds of omentum; the aorta lies beneath the third part of the duodenum.