Nothing is known of its foundation: possibly it was built on the site of an earlier residence of one of Denmark's noble families, as it would have required a donation of property for the buildings.

This location fits the usual pattern of Saint Gertrude's chapels elsewhere in Denmark at important crossroads and entrances to towns.

In 1397, during the reign of Margaret I, St. Gertrude's was being run as a religious house where weary travellers and itinerant workers could find a place to stay.

The graveyard had acquired a reputation as a place where criminals were buried, and the popular nobleman Torben Oxe was beheaded there by order of Christian II.

The only remains from the original St. Gertrude's are the large vaulted cellars beneath the present buildings at Coal Market Square (Danish: Kultorv).

During the British bombardment of Copenhagen in 1807, the tower of the hospital caught fire and collapsed into the body of the building, causing major damage.