Britain goes to the polls on June 23 to vote on whether to remain in the 28-member bloc, with major companies urging Britons to remain in the EU and retain unfettered access to Europe's market of about 500 million consumers.
Writing in the Times newspaper, Gates said he had invested around $1 billion in British research and development, attracted by the country's access to the EU single market, strong universities and heritage in science and innovation.
"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," the Microsoft founder and billionaire philanthropist said.
"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."
From U.S. President Barack Obama to the International Monetary Fund, a host of world leaders and organisations have cautioned British voters about the risks of leaving the bloc they joined in 1973.
Despite the warnings, the "Out" campaign has appeared to gain traction by focusing on the issue of migration in recent weeks. Of the seven most recently published polls, six showed the Leave campaign in the lead.
Both sides have now put their campaigns on hold since the killing of an opposition lawmaker, Jo Cox, in an attack in the street in northern England on Thursday.
(Reporting by Kate Holton; editing by Stephen Addison)
