The Esphigmenou Monastery was founded in the late 10th-century foundation on Mount Athos. Located on the north-east coast of the peninsula, 3 km east of Hilandar, the monastery is first mentioned in 998 when Theodore was hegoumenos. Its original name was Esphagmenou ("the slaughtered"), perhaps a reference to Christ, the sacrificial lamb. Esphigmenou prospered in the 11th century, acquiring vast properties on the Athonite peninsula. At this time the monastery housed a certain number of Chalcedonian Armenians, including Theoktistos, who was hegountenos in the losos and became protocol Athos around 1035. In around 1001 Nikephoros, a monk of Esphigmenou, was sent on an important mission to the Charsianon, where he founded a monastery and probably exercised influence on the recently annexed Caucasian lands. 
The establishment reached its zenith in the 14th century, when it was an imperial cenobitic monastery housing 200 monks and owning more than 12,000 mothoi of land, chiefly in Chalkidike and the Strymon valley. Among the monks who spent some time in residence there were Athanasios I, the late 13th-century patriarch of Constantinople, and Gregory Palamas, hegoumenos in 1335-36, who attempted to introduce Hesychasm into the monastery. Stefan Uroš IV Dušan issued two chrysobulls in 1346-47 confirming the monastery's titles to various properties, and granting certain tax exemptions. The history of Esphigmenou becomes obscure after the Ottomans took control of Athos in 1430. The 31 Byzantine documents preserved in the monastery’s archives range in date from 1034 to around 1409, and include early 4th-century praktika that provide information on peasant households in Macedonia. The library holds more than 100 manuscripts of Byzantine date, the most valuable of which is an illuminated 11th-century menologion with miniatures on purple parchment. The treasury contains a mosaic icon of the 14th century, depicting the blessing Christ.