Cardinal Agagianian was made a cardinal on February 18, 1946, by Pope Pius XII. He was appointed Cardinal Priest of San Bartolomeo all'Isola on February 22, 1946. Pope Pius, who had a "great interest in the Eastern churches", called on Agagianian to celebrate a pontifical Mass in the Armenian rite in the Sistine Chapel on March 12, 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 June 18, 1958, by Pope Pius. Paul Hofmann of The New York Times wrote that Agagianian, an expert on communism and on Middle Eastern problems, was appointed because he "appeared particularly qualified to combat the danger of Communist inroads in missionary areas in the Middle East, Africa and all Asia." He assumed the post on June 23 at a "simple ceremony." He became Prefect of the Congregation on July 18, 1960. The Congregation, under his direction, controlled 25,000 missionary priests, 10,000 missionary lay brothers and more than 60,000 missionary nuns worldwide. He had a staff of 27 and his jurisdiction included some 31 million Catholics, 3 million catechumens in 78 archdioceses, 197 apostolic vicariates, 114 prefectures, six independent abbeys, and three independent missions. He supervised the training of Catholic missionaries all over the world. According to Lentz, Agagianian was "largely responsible for liberalizing the church's policies in developing nations". Agagianian moved to live in Rome permanently in 1958, but he traveled extensively to the missionary areas for which he was responsible. On December 10, 1958, Agagianian presided over the First Far East Conference of Bishops at the University of Santo Tomas in Manila, Philippines with attendance of 100 prelates, 10 papal representatives, 16 archbishops, 79 bishops from almost every country in the Far East. He was Pope John's official representative at the December 8 ceremony for consecration of the reconstructed Manila Cathedral. In February 1959 Agagianian visited Taiwan to oversee missionary work in the island. He later entrusted Archbishop Paul Yü Pin to reestablish the Fu Jen Catholic University there. He arrived in Japan