The hospital was founded by David I and re-founded in 1493 by James IV at the bequest of Robert Bellenden, abbot of Holyrood.

It is notable for having served as a meeting place for the Incoporation of Hammermen and as the site of a gathering of conspirators in an unsuccessful plot to kill James V in 1529.

[1] It appears again in a bull of Pope Clement VII confirms a charter issued by Robert III in 1391, which renews a gift to the hospital of St Leonard "annexed to the barony of Brochton" and founded by David I.

[3][4] In a mediaeval and early modern context, the term "hospital" applied to institutions covering a wide variety of care and education functions.

[5] The hospital was situated on St Leonard's Hill, at the edge of the King's Park and on other side of a valley from the Salisbury Crags.

[7]The hospital may have replaced an earlier hermitage used to shelter travellers who had arrived after the closing of the town gates at night.

[13][14][15] The last building on St Leonard's Hill was erected in 1493: the date of its re-foundation charter from James IV to Robert Bellenden, abbot of Holyrood.

[16] The charter notes the hospital had "become ruined, dilapidated, and unhabitable, and unapplicable to the pious use to which it was adapted by our predecessors from time immemorial".

[22] On 2 February 1529, members of the Douglas family and allies met near St Leonard's Chapel to form their abortive plot to assassinate James V.[23][24] There are few records of the hospital's earliest inhabitants; however, the quota of six "bedemen" or "hospitallers" appears to have been maintained until the Reformation.

[1] The chaplain's manse is described in Bellenden's foundation of 1493 as "a great mansion lying beside the gate of the monastery on the north side of the high street of the Canongate": around modern-day Abbey Strand.

In 1556, shortly before the Scottish Reformation, Mary, Queen of Scots granted St Leonard's and several other religious houses around Edinburgh to the town council.

After the Battle of Dunbar, David Leslie placed cannon on St Leonard's Hill to protect his men against Oliver Cromwell's advance into Edinburgh.

[4][38][39] In the chancel, two stone coffins were discovered at the excavation along with many skeletons, which were arranged radially, like the spokes of a wheel, with the heads close to each other at the central point.

Near the east end of the chapel, a red sandstone plinth of around 2 m (6 ft) diameter was found with a hole for the bases of a cross.