The theatre was in continuous use for several centuries. However, in AD 395 the Goths invaded the Peloponnese and inflicted serious damage upon the Sanctuary of Asklepios. In AD 426, Theodosios the Great gave orders banning all activities at the Sanctuary, which saw it fall permanently out of use after almost 1,000 years of operation. Natural forces and human interventions subsequently completed the devastation. While the auditorium was buried under a thin layer of soil and preserved, the ruins of the stage-buildings, which remained above ground, were systematically looted throughout the periods of Venetian and Turkish rule. In 1881, the Archaeological Society began methodical excavations at the site, and although the stage-building was no more, the auditorium was revealed to be in good condition, with only its retaining walls missing. The theatre soon became famous, attracting the attentions of the general public. The re-emergence of the well-preserved theatre, renowned since ancient times, was closely linked to the revival of ancient drama. Pressing demands to put ancient theatres to cultural and commercial use led to a rushed and erroneous restoration of the auditorium. In 1907, the western aisle and retaining wall were repaired. The second phase of works came immediately after the Second World War, when the main aim was to shore up the monument and make it safe and suitable for summer performances of ancient drama as part of the Epidaurus Festival. This entailed extensive excavation and restoration work by the Greek Education Ministry's Department of Restoration. Conducted under the direction of Anastassios Orlandos, the work took almost a decade (1954-1963) to complete, and succeeded in ensuring the stability of all the seating in the lower tiers by completely rebuilding both of the retaining walls, and the pilaster on the east side of the entrance. Plans to repair part of the proscenium were never realized.
By 1988, three decades of intensive and unregulated use necessitated a third phase of restoration work. This was undertaken by the Committee for the Conservation of the Monuments of Epidaurus on behalf of the Ministry of Culture, and mainly consisted of corrective measures which employed strictly scientific approaches for the first time. Hundreds of seats were conserved, re-cemented, reset and replaced, access to the more fragile sections of the monument was restricted, the remains of the stage-building were protected, the auditorium's ancient drainage duct was restored, and the western gate was dismantled, repaired and reconstructed. In 1988, the theatre, along with the entire Sanctuary of Asklepios, was made a UNESCO World Heritage Site.