[3] He finished his studies before reaching the canonical age for ordination, and spent the interval as a professor of Sacred Scriptures at the College of Propaganda.

O'Connor earned a Doctor of Divinity degree following a public disputation, in which he underwent the same test made by Thomas Aquinas and Bonaventure at the University of Paris in the 13th century.

[4] He also served as an agent of the Irish bishops with the Holy See, working with Pope Gregory XVI and Cardinal Nicholas Wiseman.

[5] On his return to the United States, O'Connor passed through Ireland to recruit clergy for his new diocese, obtaining eight seminarians from Maynooth College and seven Sisters of Mercy from Dublin.

[4] To organize the new diocese, he held the first diocesan synod in 1844, and the same year he founded a girls' academy and orphan asylum, a chapel for African Americans, the Pittsburgh Catholic and St. Michael's Seminary.

[3] To serve the German immigrants in his diocese, he welcomed the Benedictine monks who founded Saint Vincent Archabbey in Latrobe, Pennsylvania,[3] the first Benedictine monastery in the United States, and to further education he invited the Franciscan Brothers of Mountbellew in Ireland, who established the first community of religious brothers in the United States in Loretto.

[5] In 1854, O'Connor was summoned to Rome to take part in the definition of the dogma of the Immaculate Conception, and it is said that changes in the wording of the decree were due to his suggestions.

[3] His health entered into a steady decline and, on the advice of his physicians, traveled throughout Europe, Asia, and North America in search of a more hospitable climate.

[3] At the end of O'Connor's tenure, the diocese contained 77 churches, 86 priests, six religious congregations, one seminary, five institutions of higher education, two orphan asylums, one hospital, and a Catholic population of 50,000.

[5] Pursuing his desire to join the Society of Jesus, he sailed for Europe the following October and was admitted into the Jesuit novitiate at Gorheim, (now part of Sigmaringen), in the Kingdom of Prussia, on December 22.