In 1511 a group of dissident cardinals called the Conciliabulum of Pisa (1511–1512) against Pope Julius II, who had ignored the electoral capitulations he had accepted before being elected.

Cajetan refused to accept Almain's argument that the Church's polity had to be similar to a lay regime, complete with limits on the ruler.

In 1518, Cajetan was sent as legate to the Diet of Augsburg and at the behest of the Frederick III, Elector of Saxony was entrusted with examining the teachings of Martin Luther.

[5] He retained influence under Pope Clement VII, suffered a short term of imprisonment after the storming of Rome by the Constable of Bourbon and by Frundsberg (1527), retired to his diocese for a few years, and, returning to Rome in 1530, assumed his old position of influence with Pope Clement, on whose behalf he drafted the decision rejecting the petition made by Henry VIII of England for the annulment of his marriage to Catharine of Aragon.

[citation needed] Appointed by Clement VII to the commission of cardinals assigned to report on the "Nuremberg Recess", De Vio, in opposition to the majority, recommended certain concessions to the Lutherans, notably the marriage of the clergy as in the Greek Church and communion in both kinds according to the decision of the Council of Basel.

[5] In the field of Thomistic philosophy, he showed striking independence of judgment, expressing liberal views on marriage and divorce, denying the existence of a material Hell and advocating the celebration of public prayers in the vernacular.

[citation needed] In this spirit, he wrote commentaries upon portions of Aristotle and upon the Summa of Aquinas, and towards the end of his life made a careful translation of the Old and New Testaments, excepting Solomon's Song, the Prophets and the Revelation of St John.

[10] Of the Reformation he remained a steadfast opponent, composing several works directed against Martin Luther,[11] and taking an important part in shaping the policy of the papal delegates in Germany.

To this study he devoted himself with characteristic zeal, wrote commentaries on the greater part of the Old and the New Testament, and in the exposition of his text, which he treated critically, allowed himself considerable latitude in departing from literal and traditional interpretations.

And from the standpoint of the Dominican idea of the supreme necessity of maintaining ecclesiastical discipline, he defended the rights of the papacy and proclaimed that the pope should be "the mirror of God on earth.

More conservative than the future School of Salamanca, his reflections were nonetheless quite modern with utilisation of practical consideration outside of pure theorical thinking and some relevant ideas, like the formulation of the liquidity preference.

Cajetan and his successors therefore, in Gilson's account, represented Thomas as focused on the forms and essences of beings only, and not on the existence of all things as participation in the pure actuality which is God.