The fire was one of the biggest disasters in London's history
Insurers would have to pay up to £65bn if there was a repeat of the Great Fire of London, new research shows.
Rebuilding an area the size of that which was destroyed in the 1666 fire would cost at least £45bn, the study by insurer RSA found.
The UK economy would be hit on a "massive" scale if the City had to close down because of fire, it said.
The study marks the 343rd anniversary of the disaster in which at least 65,000 people were made homeless.
Up to 373 acres of the City - from the Tower in the East to Fleet Street and Fetter Lane in the West - were left in ruins.
The report said: "A repeat of the City being wiped out could result in a loss in the first instance of about £3bn to the nation's economy.
"Add to that an estimated cost of between £45-65bn to the insurance industry for rebuilding the City, and then include the loss of the 319,000 City jobs, the economic ramifications of another fire on this scale would be far reaching."