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In the mid-18th century, Alured Clarke, the newly appointed Dean of Exeter proposed the idea of a new hospital in Exeter to local gentlemen. Through their funding, construction of the new hospital in the city centre area of Southernhay was completed and the hospital opened in 1743.
In 1899, the Duke of York, and his wife visited the hospital and granted it permission to use the "Royal" title.
In 1948 it became part of the newly formed National Health Service.
1974 The hospital moved to a new building on the Wonford site.