The aim of this paper is the reconstruction of the history of the competencies and activities of the Holy Office in Venice regarding Jews and Judaizers in the Modem Age and of its relations with the Venetian government who required the presence, at the side of the ecclesiastical judges, of the three Savi all'eresia, three senators representing the Republic who controlled the correctness of the action of the judges. The research is based on the proceedings held by the Holy Office of Venice against Jews and Judaizers between 1548 and 1734, the complete edition of which was published by Pier Cesare Ioly Zorattini (Processi del S. Uffizio di Venezia contro Ebrei e Giudaizzanti (1548-1734), 14 vol., Firenze, Olschki, 1980-1999). This corpus allows to perceive the attitude towards the Jews both of the Inquisition in Venice and of the Republic, who, on the whole, protected not only the Jews but also the Judaizers. In particular, in 1589, the Serenissima granted the Levantini (Eastern) and Ponentini (Western) merchants of Jewish origin a Ricondotta which, actually, allowed Judaizers to settle in the ghetto provided they declared themselves Jews, thus making it impossible for the Inquisition to prosecute them. Finally, the paper deals with the wide potentialities this corpus offers to scholars both for the knowledge of the Iberian Judaizers settlement in Venice, for the knowledge of everyday life in the ghetto and the relationship between Jews and Christians in the Republic of Venice from the sixteenth to the eighteenth century.