Starch is the most common carbohydrate in human diet consisting of a large chain of glucose units. A wide range of enzymes, called α-amylases, catalyze the hydrolysis of starch to yield lower molecular weight sugars, by cleaving the α(1-4) glycosidic linkages. The human being has two different amylases, one in the saliva (HAS) and the other in the pancreas (HPA). In this work we studied the catalytic mechanism of the human pancreatic α-amylase. Our final goal was to determine the catalytic mechanism of the HPA with atomic detail, using computational methods. We demonstrated that the HPA catalytic mechanism consisted of two steps, in which the first mechanistic step (glycosylation step) involved the breaking of the glycosidic bond that culminated in the formation of a covalent intermediate. The second step (deglycosylation step) completed the hydrolysis of the sugar. Since the active site was very open to the solvent around the protein, our mechanism basically differs from the previously proposed mechanism for having two water molecules instead of only one near the active site. We also demonstrated the relevant role of the three catalytic amino acids, two aspartate residues and a glutamate (D197, E233, and D300) during catalysis. It was also shown that the rate limiting step was the glycosylation step, and its activation energy was in agreement with the experimental values obtained for the HPA. The experimental activation energy was 14.4 kcal.mol<-1> and the activation energy obtained experimentally was 13.9 kcal.mol<-1>.