Royal Bank of Scotland said it would relocate to London from Edinburgh if Scotland votes for independence from the United Kingdom next week.
RBS has been based in Scotland since its formation in 1727.
It has stated that it intended to retain a significant level of its operations and employment north of the border.
"RBS believes that it would be necessary to re-domicile the bank's holding company and its primary rated operating entity (The Royal Bank of Scotland plc) to England," it said in a statement reported by international media.
Meanwhile, Lloyds Banking Group, which owns the Bank of Scotland, is to move its headquarters from Edinburgh to London in the event of a Yes vote in the independence referendum.
With a history dating to 1695, it is the second oldest surviving bank in the United Kingdom, only one year younger than the Bank of England.