| Summary: | <p class="Body">Alexander the Great’s cause of death has been contentious since antiquity. Historians and physicians alike have proposed a multitude of hypotheses. However, neither party is without their analytical flaws. The historians often neglect obvious medical refutations. Meanwhile, the physicians often err by forsaking disciplined historical methodology. Therefore, the authors of this paper subject these prior hypotheses to both medical and historical criticism, in order to provide a multidisciplinary approach to a longstanding mystery. Some hypotheses have more weight than others, as is discussed. The most probable of the poisoning hypotheses, which aligns with the Vulgate tradition of Alexander’s death, cites the use of <em>Veratrum album, </em>a plant derived bane<em>. </em>When the Court tradition is considered, <em>i.e. </em>that<em> </em>no foul play occurred, acute pancreatitis induced by alcohol abuse holds greatest credence as a hypothesis. It is hoped that the approach used will not only increase clarity regarding Alexander’s death and challenge weak ideas but also provide an approach by which speculation about other medical diagnoses in history may be tempered and critiqued.</p>
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