The UK would suffer a "serious economic shock" in the event of a Brexit, with a cost of £100 billion and one million jobs, the CBI has warned.
The business lobby group, which represents around 200,000 businesses, said a vote to leave the EU would have "negative echoes" for many years.
Carolyn Fairbairn, director general of the CBI, said a Brexit "would be a real blow for living standards, jobs and growth".
She added: "The savings from reduced EU budget contributions and regulation are greatly outweighed by the negative impact on trade and investment.
"Even in the best case this would cause a serious shock to the UK economy."
On behalf of the CBI, accountancy giant PwC forecast average annual economic growth to be 2.3% between 2016 and 2020 if the UK stayed in the EU. However, if it left the Union, PwC said economic expansion would be 1.5% under a Free Trade Agreement, and just 0.9% if the UK traded as a member of the World Trade Organisation.
Speaking to the BBC, Ms Fairbairn said: "You might call it an uncertainty shock over the next five years that reduces the GDP of the economy by 3%, [and] delivers an increase in unemployment of about 500,000.
"And even in the longer run the economy would stay smaller than it would have been otherwise."
If the UK stays, PwC expects employment to rise to 32.2 million by 2020. But the number of people in work could fall by 550,000 in the event of a Free Trade Agreement, and by 950,000 in a World Trade Organisation scenario.
PwC said it would take at least two years to establish and negotiate a new relationship with the EU, which would lead to "significant economic and political uncertainty".
Ms Fairbairn said: "The economy would slowly recover over time, but never quite tracks back to where it would have been. Leaving the EU would mean a smaller economy in 2030.
"There is no clear description of what kind of alternative is on the table.
"The European Union has no particular rush to want to do a deal with us, and we'd have to renegotiate 50 deals around the world that are currently run through the European Union."