I propose that Alexander the Great died of acute pancreatitis secondary to heavy alcohol consumption and a very rich meal. The cause of death of prominent historic or artistic figures attracts considerable interest of historians and researchers. This is especially the case for Alexander the Great. More than 20,000 publications, books, or monographs on the life and work of Alexander the Great have been published. There are several theories and hypotheses regarding the cause of his death, that are based on historic descriptions, diaries, notations, and interpretations of events. It is inevitable that history and myth intermingle in any investigative approach, no matter how scholarly. In this article, on the basis of several historic sources, I have made an effort to reconstruct the final 14 days of his life and record the course of medical events that preceded his death with the formulation of a plausible diagnosis.