Spyridon eventually became Bishop of Trimythous, or Tremithous (today called Tremetousia), in the district of Larnaca.

The relics were found to be incorrupt, and contained a sprig of basil, the "royal plant," both of which were taken as a sign of divine confirmation of his sanctity.

This time, they were taken to the island of Corfu by a Corfiote monk called Kalohairetis (Καλοχαιρέτης), where they remain to this day, in Saint Spyridon Church.

The relic of his right hand was located in Rome in the Church of Santa Maria in Vallicella, to which it was given by Pope Clement VIII to Cardinal Cesare of Baronio of the Oratory of Saint Philip Neri.

It is believed by the faithful that the plague, on its way out of the island, scratched one of the fortification stones of the old citadel (Palaio Frourio) to indicate its fury for being expelled.

At that time the Turkish army and naval force led by the great Sultan Achmet III appeared in Butrinto opposite Corfu.

After repeated failed attempts and heavy fighting, the Turks were forced to raise the siege which had lasted 22 days.

There were also rumors spreading among the Turks that some of their soldiers saw Spyridon as a monk threatening them with a lit torch and that helped increase their panic.

The Grand Prince of Muscovy Basil II (1425–1462) apparently gave a gold cross containing relics of the saint to Andrei.