Significant damage seems to have been caused by an earthquake in 1446, but the church was quickly restored. In 1557 it was almost completely rebuilt from the foundations, after the great fire of 1554. With the reconstruction in 1557 it acquired a square basilica with a central dome, and a bell tower in the southwest corner. It was converted into a mosque during the Turkish occupation.
This building was destroyed by the great earthquake of 1856, and was rebuilt from scratch from plans drawn up by the working architect Athanassios Moussis, who designed the cathedral of Agios Minas. The church continued to function as a mosque until about 1922. In 1925, after undergoing repairs and modifications, it became an orthodox church again, some 700 years after the conquest of Crete by the Venetians and the subsequent occupation by the Turks.
Today, Agios Titos and the square of the same name where it stands is one of the most beautiful places in the city of Heraklion, with a large plane tree towering over the buildings of the Loggia and the church.