As a result of the English Reformation, Cole initially conformed to Anglicanism, but returned to Catholicism in about 1547 resigning all his preferments (titles of religious office) in the newly-formed Church of England.
He became Archdeacon of Ely, a canon of Westminster (1554), a vicar-general of Primate of All England Cardinal Reginald Pole (1557), and a judge at the archiepiscopal Court of Audience at Canterbury Cathedral.
Cole was one of the commissioners who restored Cuthbert Tunstall and Edmund Bonner to their bishoprics, and was disputant against Thomas Cranmer, Nicholas Ridley, and Hugh Latimer at Oxford (1554).
In 1558, just months before the death of Mary I, Cardinal Pole commissioned Cole (as Dean of St Paul's Cathedral) to suppress the heresy of Protestantism in Ireland.
Cole showed the mayor a leather box, which contained his letters of authority from Cardinal Pole, saying "Here is what will lash the heretics of Ireland!"
Cole only discovered the deception when he opened the box to much surprise at an assembly in Dublin Castle in front of the Lord Deputy of Ireland Thomas Radclyffe and members of his Privy Council.
[6] Cole remained true to his Catholic faith despite the new queen immediately changing the country's religion back to Protestantism.
Only six weeks after the end of the conference, Cole was fined 500 marks for being a practising Catholic, deprived of all his Church preferments (ie titles, positions, prestige), and sent to the Tower of London on 20 May 1560.