The Hospice of Aghia Aikaterini, situated within the medieval town of Rhodes, was built in 1391-1392 under grand master Heredia, by the Italian Domenico d'Allemagna, admiral of the Order of the Knights of St. John (Knights Hospitaller), an eminent and rich member of the local aristocracy of the period. The contract of the foundation of the hospice, dated in 1391, states that the building is located “within the burgus of Rhodes, near the walls at the gate leading to the mole”. Later on, in 1465 another document refers to it as the “Gate of Aghia Aikaterini”.

The building is very impressive and holds a central place along the axis of the square that gathers all the commercial activities of the town. The building had been constructed to house the official and eminent guests of the Knights during their staying in Rhodes, as we are informed by the Italian traveler Niccole de Martoni, who visited the island in 1395; he also adds that it is «beautiful and splendid, with many nice rooms and good beds». During the siege of the town by the Ottomans in 1480 and the earthquake that followed in 1481, the building suffered extensive destruction. It was rebuilt, a process that lasted up to 1516, when Grand Master was Costanzo Operti, as it is evidenced by the walled-in blazons, preserved up to now.

During the World War II, in 1944, the eastern part of the Hospice collapsed by Allied bombing, along with many buildings in the center of the Jewish quarter. After the bombing, the building, semi-ruined, stood forlorn within an abandoned neighborhood. The preserved part was occupied by homeless immigrants from the nearby islands, who lived there in miserable conditions. This situation lasted until 1986, when the Hospice along with the 20 buildings, state-owned properties, entered in the restoration program of the Office of the Medieval Town, which had been founded in October 1985.