Agagianian was made a cardinal on 18 February 1946, by
Pope Pius XII. He was appointed Cardinal-Priest of
San Bartolomeo all'Isola on 22 February 1946.
Herbert Matthews noted that it was Pope Pius's "desire to emphasize the universality of the Catholic Church". Held in commemoration of the seventh anniversary of the Pope's coronation, it was the "first time any but the Latin rite has been used in the Sistine Chapel". Pius named him a member of the
Holy Office in June 1958.
Prefect of Propaganda Fide Agagianian was appointed Pro-Prefect of the
Sacred Congregation for the Propagation of the Faith (
Propaganda Fide) on 18 June 1958, by Pope Pius. He assumed the post on 23 June at a "simple ceremony". He became Prefect of the Congregation on 18 July 1960. He was Pope John's official representative at the 8 December ceremony for the consecration of the reconstructed
Manila Cathedral. In February 1959 Agagianian visited
Taiwan to oversee missionary work on the island. He later entrusted Archbishop
Paul Yü Pin to reestablish the
Fu Jen Catholic University there. He arrived in Japan for a two-week long visit in May 1959, which included a meeting with Emperor
Hirohito. His visit to Ireland in June 1961 was the highlight of the Patrician Year, when the 1,500th anniversary of
Saint Patrick, Ireland's patron saint, was celebrated. Agagianian received a great popular welcome there.
Fianna Fáil President of Ireland
Éamon de Valera was famously pictured kissing Agagianian's ring. Agagianian celebrated a pontifical high mass in Dublin's
Croke Park attended by more than 90,000 people. In September 1963 he met with
Madame Nhu, the Catholic first lady of
South Vietnam, in Rome. On 18 October 1964, when the
Uganda Martyrs were canonized by Pope Paul VI, Agagianian presided over the Holy Mass at
Namugongo. In November 1964 he traveled to
Bombay, India to open the 38th
Eucharistic Congress. It was attended by more than 200 cardinals and bishops.
Second Vatican Council Agagianian sat on the Board of Presidency of the
Second Vatican Council (Vatican II), which took place from 1962 to 1965. He was appointed by
Pope Paul VI as one of the four moderators who directed the course of the debates, Agagianian was the only one of these four from the
Curia, and represented the
Eastern Catholic Churches. He had a special role in the preparation of the missionary decree
Ad gentes and
Gaudium et spes, the Constitution on the Church in the Modern World. ==Papal candidate==