The Edinburgh Hospital for Sick Children first opened in 1860 at no.7 Lauriston Lane. It had 20 beds and a dispensary. In 1863 Queen Victoria bestowed upon it her Royal Patronage. In the same year the hospital moved to larger premises in Meadowside House, at the foot of Lauriston Lane. The move doubled the capacity. In 1870 the addition of a new wing increased the number of beds to 72.

In 1890 an outbreak of typhoid fever in the hospital affected several members of staff and caused the death of a nurse. This and other factors made the Directors decide to move the hospital to other premises while Meadowside House was thoroughly examined. They managed to secure the lease of Morningside College at Plewlands.

A thorough inspection revealed the Meadowside House did not have all the necessary facilities for the work of a hospital. The building was demolished and the site sold to the Royal Infirmary. The Directors then purchased the Trades Maidens Hospital at Hillbank, and demolished that building. On the site thus cleared a new children's hospital was built to the design of G.Washington Browne. This, the present Royal Edinburgh Hospital for Sick Children, was formally opened by Princess Beatrice on 31st October 1895.

In 1906 the hospital received the bequest of the estate and house of Muirfield. The existing house was initially used as a Convalescent Home, but it proved to be too small, and so it was demolished and a new Home, built to R.S.Lorimer's designs, was formally opened on 17th July 1909. It could accommodate 24 patients. Muirfield Convalescent Home could take children over the age of two years. There was a need for a Home for very young children, and this need was met in 1934, thanks to the generosity of Lord Forteviot and the Dewar family. The Directors were able to purchase the house at no.16 Hope Terrace. It was opened on 23rd January 1936 by Lord Forteviot and had cots for 16 patients. In 1948 the adjacent house was purchased and the Home extended.

In 1948 the Hospital became part of the Edinburgh Central Hospitals group under South Eastern Regional Hospitals Board. From 1974 to 1984 it came under the South Lothian District of Lothian Health Board. It is now known as Edinburgh Sick Children's NHS Trust Hospital.