Mr McEwan said the UK vote to leave the European Union has not changed the bank’s position in 2014 that it may have to move out of Scotland in the event of independence.
First Minister Nicola Sturgeon has pledged to explore all options to keep Scotland in the EU, and said a second independence referendum is “highly likely”.
Some experts have suggested Scotland’s financial services sector could benefit from Scotland’s continuing membership of the EU, providing a new gateway to the European single market for British businesses after the rest of the UK leaves.
Mr McEwan said RBS would be “too big for the economy” in an independent Scotland and it may have to register elsewhere, but that the move would not affect the 12,000 people who work for the bank.
He told the BBC: “We’d have to make the same moves I suspect because the Royal Bank of Scotland, being domiciled in Scotland, would just be too big for the economy, even in the shape that we’re building.
“That’s around the plaque, it’s not about where our people are because we have a very big business up here in Scotland.
“I’ve got 12,000 people who serve both the Scottish people and we also run our retail business from up here along with a lot of our technology.
“Two years ago when we had the Scottish referendum, I made it very clear we’d have the people in the right place, that moving the plaque didn’t make any difference to them.
“I think that would be the same. I think for any country, they just need to remain very competitive so businesses like ourselves want to operate in those countries.”
Asked what he would say to Ms Sturgeon if she wanted his views on the economic impact of a second independence vote, he replied: “Just take account of uncertainty - that’s what you’re seeing after Brexit.
“It’s uncertainty that slows markets down. Make sure the long game’s worth it. But that’s going to be up to the people of Scotland.”
A Scottish Government spokeswoman said: “As RBS has made clear, the location of their ‘brass plaque’ will make no difference to jobs in Scotland.
“The uncertainty our economy faces is from Brexit. That’s why our immediate priority is to secure our continued place in the single market and maintaining and strengthening our links with our key European markets.”