If still in use by the 4th century AD, the temple would have been closed during the persecution of pagans in the late Roman Empire, when the Christian Emperors issued edicts prohibiting non-Christian worship.

In 1988, the temple was inscribed on the UNESCO World Heritage List because of its exceptional architecture and its importance in the development and spread of healing sanctuaries (asclepeia) throughout classical antiquity.

The 2nd century AD geographer Pausanias described the myth around the foundation of the temple, as well as its religious significance to the worship of Asclepius (Description of Greece 2.26-28).

[4] After Lucius Mummius defeated the Achaians and destroyed Corinth in 146 BC, he visited the sanctuary and left two dedications there.

[5] Livy, in the early first century AD, speaks of how "Epidaurus ... was once rich with gifts for the god, which are now vestiges of wrecked dedications.

"[6] Inscriptions claim that the town was rescued from total destruction by a series of gifts from a rich benefactor, Euanthes son of Eunomus, who was honoured with at least six monuments.

[8] Hadrian introduced a range of reforms, apparently influenced by the cult of Asclepius at Pergamum, which he was closely involved with.

[13] Most notably, Pythodorus carried out extensive repairs to the Sanctuary of Apollo Maleatas, which had been abandoned since the early first century BC, adding a propylon, a nymphaeum, and a vast subterranean cistern ("the Skanà").

These, the work of master sculptors of the period, occupy a prominent room in the National Archaeological Museum at Athens.

It was a site for holy pilgrimage from the entire ancient world, and influenced the worship of Asclepius in many other sanctuaries dedicated to him.

Cicero alluded the merciful nature of Asclepius when he recounted how Dionysius I of Syracuse allegedly committed sacrilege at the sanctuary without divine punishment: "He gave orders for the removal of the golden beard of Aesculapius at Epidaurus, saying it was not fitting for the son to wear a beard when his father [Apollo] appeared in all his temples beardless...

[22] The stelae, dating to the late fourth or early third century BCE[23] and sometimes called 'miracle inscriptions',[24] recorded the names of at least twenty individuals and the means by which they were healed – usually miraculous dreams or visions.

[27] In 1884, he excavated the Temple of Artemis and the Great Propylaia,[21] and reconstructed a row of columns in the western stoa of the abaton.

[35] Kavvadias's report on his excavations of the Roman-period odeion at the site, which he published in 1900, has been described as "invaluable" for the amount of evidence it preserves, much of which has been lost through later deterioration in the building's condition.

The findings from the building's excavation were never fully published; in 1992, the archaeologist Stephen G. Miller suggested that it may have been an apodyterion (changing room) for the athletes.

[43] The excavation of Epidaurus has been described as a "landmark", both for its place in the institutional history of Greek archaeology and for the finds uncovered there.