Landing at Colon, he crossed the Isthmus of Panama, then part of New Granada. Vaughan arrived in Panama amidst a conflict between church and government - the latter demanding the renunciation by the former of civil powers. The clergy were forbidden to say mass or to administer the sacraments until they had taken an oath to accept the Constitution, which required what was regarded as an acknowledgement of the supremacy of the civil power in spiritual matters. Churches had been closed by the government and though hundreds of people were dying of small-pox, they were left to die without the help of a priest. Vaughan immediately set about providing services despite government warnings. Eventually, after ignoring a direct warning from the president, Vaughan gave Viaticum to a dying woman, and was arrested and required to post bail. Realizing that no more could be done in Panama for the time, Vaughan jumped bail and at once went on board a United States steamer and sailed for San Francisco.
On 1st February 1864, Vaughan arrived to a cool reception from the Dominican Archbishop. Here, in spite of the limitations put to his appeals for money, during a stay of five months he succeeded in collecting $25,000. From California he went back to Panama, intending to beg his way through Peru and Chile, then ride across the Andes into Brazil and thence to sail for home or for Australia. In Peru he collected $15,000, and nearly twice as much in Chile. In March, 1865, he left the cities of the Pacific but, instead of crossing the Cordilleras, he sailed round the Horn in "H.M.S. Charybdis". A month later, he arrived in Rio. The high point of this final stop on his South American tour was the offer on the part of Emperor Pedro II and his Empress to become patrons of his project and their gift of a thousand Brazilian dollars. During the ensuing tours through California, back to Panama, Peru, Chili, and Brazil, Vaughan raised over $40,000.
While at Rio, he received news that Cardinal Wiseman had died. He also received news that the Oblates were planning to establish a seminary of their own in Rome so he began to seriously think about a separate missionary college of his own. In May 1865 in Rio de Janeiro, Vaughan made his decision: with the approval of Manning he would start at once by renting a house in or near London.
In June his campaign was brought to an abrupt close by a letter of recall from Manning, who had just been appointed Archbishop of Westminster, and Vaughan sailed for England in June, 1865. He put his plans together on the journey home. His college would be called ‘College for Foreign Missions under the patronage of the Sacred Heart of Jesus’. His Congregation would be one of secular priests bound together by a common rule, and with an obligation to leave Europe. The Holy See would be petitioned to assign a mission not already established, hopefully part of Japan, and his missionaries would be sent out under the Bishop of that place.
Vaughan arrived in Bordeaux in the last week of July 1865 and set off for England via Paris where he prayed at Notre Dame des Victoires. At Kensington, Archbishop Manning received him kindly and encouraged him to devote all his energies to the foundation of a missionary college.