The next care of the reformer was to petition the king for a seminary wherein the ranks of the clergy, thinned almost to extinction, might be reinforced by men carefully trained to a due appreciation of their high calling. The result was the foundation of the seminary of priests of noble family, recruited mainly from the college which the Jesuits had opened at Vienna, and to which had flocked students from all the great families of Hungary, Bohemia, Poland, etc. In conjunction with this seminary, St. Ignatius, about the same tune, founded the celebrated German College in Rome, for the regeneration of Germany by means of a clergy that should be as learned as it was morally irreproachable.

In the midst of his multifarious occupations, Canisius continued his sermons at court, in the Cathedral, and in the principal churches of Vienna. Lutherans frequented them largely, and some, touched by the power of his doctrine and eloquence, asked him for conferences, which he gladly accorded them. Among these were two preachers of some celebrity, pillars of Protestantism, who defied him to answer their arguments in a public disputation. He accepted the challenge, and the day, place, and hour were fixed. A great concourse of people, composed largely of the new sectaries, were assembled, prepared to swell the expected triumph of their champions. The two heretical doctors held their dissertations, one after the other, and sat down amid the applause of their sympathisers. Then Canisius stood up with religious modesty and humility, his bearing expressive of the calmness and benevolence of one who has the whole Catholic Church, past and present, on his side. His prodigious memory and profound knowledge enabled him to refute easily every charge brought by his adversaries, whom he completely crushed with the overwhelming consistency of his logic. They both acknowledged themselves defeated; one returned to the Catholic Church, and a few months later entered the Society of Jesus, of which he remained an edifying member till his death; the other became a more determined advocate of heresy than before, and swore to avenge his defeat by a persistent persecution of the Jesuits.

Nor were enemies wanting on any side; the more converts the Jesuits made, the greater was the hatred they inspired. Calumnies were sown broadcast, and the life of Father Canisius was in constant danger. Ferdinand, warned of a plot to murder the holy man, obliged him, greatly to his discomfiture, to accept a bodyguard whenever he went out. But the work of reform and conversion went on steadily, and from all parts of Germany, bishops, princes, and governors sought to obtain the presence of the illustrious apostle. "I am ready," he wrote in this regard to St. Ignatius, "to go wherever obedience calls me, and to work for the salvation of souls however abandoned they may be, whether in Poland, Lithuania, Russia, Tartary, or China, wherever I am sent."

He was sent to Prague, perhaps the most God-forsaken spot in the whole empire. Every imaginable sect had accumulated in Bohemia during the preceding twenty years. Scarcely a vestige of Catholicism remained, and Hussites, Wicklifites, Vaudois, Lutherans, Zwinglians, and various other offshoots of the principal sects, were busy relegating each other in eloquent terms to eternal damnation, when the arrival of Catholic missionaries gave the signal for a coalition against the common enemy of them all. At Prague itself, where Canisius was charged to found a college with the injunction not to leave Bohemia until it should be solidly established and in a flourishing condition, the Hussites outnumbered the others. Scarcely had he arrived and set to work, when the Duke of Bavaria, reminding St. Ignatius that Canisius had only been lent to Austria, claimed him, at least temporarily, for the foundation of the college which the Society was to establish at Ingolstadt. The claim was admitted to be just, and accordingly the affairs of Prague could only be proceeded with four months later, when Canisius returned from Germany, having been made provincial.

It was the beginning of Lent 1555, and on the 21st April twelve priests sent to him from Rome by St. Ignatius, arrived to second him in his perilous undertaking. The first time the Jesuits appeared in the streets they were saluted with handfuls of mud cast at them by the city urchins, who had been bribed to insult them. The cry "Dogs of Jesuits" (a play upon the word Canisius) followed them wherever they went. Father Peter was himself assailed with a large stone hurled through the window of the church as he stood at the altar saying Mass. A plot was formed to throw the whole community one by one into the Moldau, as they passed over the bridge that connected the old and the new town; and ruffians, who had received a part of their reward in advance, were stationed in the middle of the bridge to waylay them. But a timely edict issued by the Archduke of Bohemia threatened with the most severe penalties whoever should raise a hand against any member of the Society, or even treat any one of them disrespectfully. He went still further, and sent a detachment of guards to the college daily, with orders to accompany each of the priests wherever he went, and in sufficient numbers to prevent any attack.

Added to the open enmity and fierce hatred which they inspired, the Jesuits had to encounter the jealousy of the University professors, who would have been willing enough that they should preach, but who, on the opening of their college, did all they could to hamper them and prejudice people against them.

The reputation of the Society for teaching was great all over Germany. Wherever a college was established by them, it immediately attracted students from all parts, and it was perhaps natural that other educational institutions should fear for their own existence. But the pettiness and meanness with which this fear was expressed at Prague resulted for the Jesuits in a penury so abject, that for many months they had nothing to eat but bread and cheese, and nothing to drink but water from their own well. For several days they were even prevented from going out for want of suitable garments. Nevertheless, however much they might have to suffer in any one place, struggling through a painful existence to the end in view, the work of reform went steadily forward.

About this time, the cathedral at Regensburg was in need of a preacher; the Diet was about to assemble in that city, all the princes and electors of the empire were to take part in it, and the new sectaries were expected in great numbers, in order to wrench, if it might be, such concessions from the authorities as they had not yet been able to obtain. The chapter therefore appealed to Father Canisius, and besought him to throw himself into this important breach. Realising all that was at stake, he started at once for Regensburg.

His first appearance in the cathedral pulpit was a splendid testimony to the opinion in which he was held. The vast building was filled with a brilliant throng, on the fringe of which the people hung in dense crowds overflowing into the streets. In a letter to Father Lainez (who had succeeded St. Ignatius as General of the Society) in September 1556, Canisius describes his efforts as successful in supporting and strengthening the persecuted Catholics, but he goes on to say that the Lutheran representatives at the Diet let loose a string of calumnies against him, and did all they could to poison the minds of the weak and simple. But for the States of the Empire they would have cast him out of the city as one so dangerous to the Protestant cause that they declared it would be wrecked altogether if Canisius continued to preach there.

However, continue he did during the whole of the sessions, save for a short interval of absence. In this interval he visited Innsbruck, in which town a college of the Society was nearing completion; and Augsburg, whose bishop, his old friend the celebrated Otto Truchsess, desired to consult him on the affairs of his diocese. There, overwhelmed with his almost superhuman labours, Canisius fell ill. He desired to be taken to the college at Ingolstadt, and Cardinal Truchsess accompanied him thither, while the Duke of Bavaria sent him his physicians. Thanks to their skill and to the enforced rest of his mental and physical powers, he soon recovered, and was able on the 1st December to return to his post at Regensburg. On all the Sundays of Advent he preached at the cathedral, but as it could not contain the vast concourse of people who crowded to hear him, he was obliged to preach three times in the week also. From the pulpit he went to the confessional, and when he returned to his lodging he was besieged by those who came to seek his advice-princes, concerning the interests of religion in their dominions, prelates, in regard to the reform of their dioceses, or to their own spiritual needs. The King of the Romans, and the Duke of Bavaria often sent for him to confer with him, and all admired the humility, simplicity, and patience with which he listened, no less than the frankness and freedom from human respect with which he proffered his advice. But time was wanting for all the demands made upon him; and that all might be satisfied he drew up for the use of bishops a short treatise on the means of reforming the clergy, and of introducing good morals among their flocks.