His most well-known book in three volumes, Quæstiones medico-legales (1621–1651), established legal medicine as a topic of study.

[2] Zacchias took a skeptical approach that attempted to eliminate natural causes before diagnosing phenomena as witchcraft.

[6] Under Emperor Charles V of the Holy Roman Empire in 1532, legal medicine was introduced to the court system via penal code.

However, Zacchias's work helped to add scientific basis to the legal practice and court system.

[6] Since 2008, a collaborative online project of scholars has been crowd-sourcing an English-language translation of the 85 Consilia at the end of this important book.