Bill Gates has said Britain after Brexit would be a "significantly less attractive place to do business and invest".
The world's wealthiest man, who has invested more than $1 billion in the UK, offered the stark warning a day after some polls suggested the Leave campaign had edged ahead.
In a letter to The Times, he said Britain would be "stronger, more prosperous and more influential" inside the EU.
Mr Gates, who founded Microsoft and the Bill and Melinda Gates Foundation - a philanthropic organisation - also said Britain's EU membership and access to the single market played a role in the decision to place the company's research facilities in Cambridge.
He said: "While ultimately a matter for the British people to decide, it is clear to me that if Britain chooses to be outside of Europe, it will be a significantly less attractive place to do business and to invest.
"It will be harder to find and recruit the best talent from across the Continent; talent which, in turn, creates jobs for people in the UK.
"And, it would be harder to raise the investment needed for public goods such as new medicines and affordable clean energy solutions, for which we need the scale of collaboration, knowledge sharing, and financial backing that the combined strength of the EU provides."
Meanwhile, Russian President Vladimir Putin questioned why British Prime Minister David Cameron called the referendum.
"If it's such a problem, why did he initiate this, if he is against it himself?" Mr Putin said of Mr Cameron at a meeting on the sidelines of the St Petersburg International Economic Forum.
Mr Putin said that he had a view on whether Britain should leave the EU but that it was not appropriate for him to voice it because it was Britain's internal affair.
