Between 398-404 John Chrysostom, bishop of Constantinople, developed a similar institution, having physicians but still offering food and shelter to the poor and strangers.

Several xenons arose in other cities, some run by monks, some supported by wealthy citizens, often receiving privileged tax treatment from the government.

Between 420 and 650 hospitals became more numerous and larger, found in Ephesus, Edessa, and Jerusalem (200 beds), sometimes now run by medical doctors. The famous Sampson Xenon, first opened in the late fourth century in Constantinople, was rebuilt after AD 532 into a multistoried complex of elaborate buildings where patients were treated in wards by specialized physicians.

By A.D. 650 some hospitals were also beginning to treat patients who could pay, in one case even the sister-in-law of the empress. Eventually large hospitals, such as that founded by Empress Irene (797-802), developed in several cities, especially in Constantinople.

The most famous of these, the Pantocrator Xenon, is especially important because its charter (Typikon) is the only one to have survived and provides detailed information of how it was constituted and managed. Founded in 1136 by emperor John II Komnenos, it overlooked the Golden Horn on the site now occupied by the Zeyrek Kilisi Mosque. It was attached to the monastery of Christ the Savior Pantokrator (the Ruler of All) and funded by the imperial authorities, thus no longer having to rely on support from the church. It had 50 to 70 beds with pillows and clean sheets, the beds arranged into five sections. Two sections were designated for wounds and fractures, the others for medical conditions of the eyes or intestine, for women’s illnesses, and for men with diverse conditions. Each section had an extra bed to provide for overflow, bathing facilities, separate latrines for men and women, and perforated mattresses for the incontinent. Patients received a diet of bread, vegetables dressed with olive oil, extra onions, and they were given some money to buy wine or extra food.