This book explores the causes of prosecutorial independence and effectiveness against systemic corruption through an examination of the conditions leading to the Italian “Clean Hands” operation’s unprecedented success. In 1992, Italian prosecutors uncovered a decades-long corruption system cutting across regions and levels of government. The Clean Hands operation resulted in hundreds of convictions and permanently changed the Italian political landscape. This judicial breakthrough derived from a gradual and conflictual process to replace hierarchical prosecutorial institutions with more egalitarian ones. The author shows via case studies of the prosecutors’ offices in Milan, Rome, Palermo, and Reggio Calabria that the introduction of egalitarian decision-making afforded local prosecutors with enhanced independence in exploring novel investigative techniques and legal theories. The introduction of egalitarian organizational structures created ideal conditions for the emergence of legal innovations and their diffusion via judicial and prosecutorial networks. This process resulted in the unprecedented accumulation of prosecutorial expertise on complex criminal issues, such as domestic terrorism and mafia organizations, and led to the emergence of an effective prosecutorial approach to systemic corruption. Thus, the Italian case offers important lessons that may apply to the prosecution of systemic corruption in other democracies as well.