Between August 1424 and Lent 1425, during the Anglo-Burgundian alliance when John Duke of Bedford ruled Paris as Regent after the deaths of Henry V of England and Charles VI of France, a mural of the Danse Macabre was painted on the back wall of the arcade below the charnel house on the south side of the cemetery.

[1][4] The well known anatomist Andreas Vesalius made several night visits in the cemetery (and the Gibbet of Montfaucon) to study the bones there and bring it home with him.

[6] During the reign of Louis XV, inspectors recorded accounts of the difficulties in conducting business in the area due to the unsanitary conditions of the cemetery, caused by overuse and incomplete decomposition of bodies.

Two edicts by Louis XVI to move the parish cemeteries out of the city were resisted by the church, which was operating from burial fees.

[7] Many bodies had incompletely decomposed and had reduced into large deposits of fat ("corpse wax", or adipocere), chiefly in the form of palmitic acid.

[1] At its closure, it was estimated that from the Middle Ages until the eighteenth century the Holy Innocents' Cemetery had been the repository of corpses from 22 parishes in Paris, including the remains of those who died at the Hôtel-Dieu, plague victims, and various unknowns who drowned in the Seine, died on the roads, or were crippled at the nearby crossroads of the "Court of miracles", for a total of about two million Parisians.