[1] The hospital has its origins in a leper house and church named St. Stephen's which was established on the site pre-1230 AD and which had come under the jurisdiction of an unnamed religious brotherhood by the late 14th century.

The charitable offerings of the citizens of Dublin to the institution diminished during the Elizabethan era and an entry in the Assembly Rolls of the Corporation of 1590-91 describes how "the poor lazares (lepers) of St. Stephen's complaineth that they are in distress and wante".

[3] Somewhat of an effort was made between 1697 and 1698 to revive the hospital in some form, and permission was granted by the Churchwardens to "build a house containing four rooms for poor decayed Christians" on the ground "adjoining the gate of St. Stephen's Churchyard which is now walled in and made parte of the said churchyard, but on which ground, or thereabouts, there was formerly a poore house built.

In May 1734, with the advice, direction & consent of the aforementioned St. Peter's committee, Mercer assigned unto a number of eminent surgeons the running of the facility who subsequently converted it into a hospital for patients suffering from "diseases of tedious and hazardous cure, such as falling-sickness, lunacy, leprosy, and the like".

[4] Before Mercer had opened her hospital fully, Sir William Fownes, a wealthy landowner and MP for Wicklow, had petitioned Dublin Corporation in 1734 (alongside a group of doctors and clergymen) seeking money to turn Mercer's former school and almshouse into a designated hospital for 'lunatics, or such other poor people whose distempers are of tedious or doubtful cure, such as persons affected with cancers, king's evil, leprosy, falling sickness, etc'.

The most significant of these was the first performance of Handel's Messiah, which took place in Neale's Musick Hall in Fishamble Street on 13 April 1742.

[11] In the late 1880s trouble broke out among the staff, leading to charges being brought against Dr. O'Grady, senior surgeon at the hospital.

[14] The hospital closed in 1983 and was acquired by the Royal College of Surgeons in Ireland who converted it into a clinical centre and medical library in 1991 keeping on the original front granite facade of the Georgian and Victorian buildings.