As a member of the Venetian Senate, and a man of "grand experience", he was unanimously elected on 7 February 1492 to replace Girolamo Donà as ambassador to the Holy See. He was accompanied to Rome by the newly elected ambassador to Ferdinand I of Naples, Niccolò Michiel, entering the city on 26 May. With the death of Pope Innocent VIII soon after, his mission acquired new importance, as the selection of a new pope could tilt the precarious political balance in Italy. Cappello played the diplomatic game well, publicly affirming the impartiality of the Republic, while being an active participant in the backroom dealings prior to the conclave, as well as in the affair of the eligibility of the Patriarch of Venice, Maffeo Gherardi, as a voting member of the conclave.