Eurosceptic MPs attacked by business leaders
Those calling for the UK to leave the EU are "putting politics before economics", business leaders have said.
In a letter to the Independent, figures from BT, Shell, Lloyds Banking Group and Deloitte, estimated membership was worth up to £92bn a year to Britain.
But the 19 signatories accepted reforms were needed and urged David Cameron to protect the City from EU ideas which they said put its standing at risk.
The move comes amid splits within the Conservative Party over Europe.
On Sunday, Tory grandee Lord Howe accused the prime minister of "running scared" of Eurosceptics and losing control of his party on Europe.
But Health Secretary Jeremy Hunt said the party was united and Mr Cameron was showing leadership on the issue.
The prime minister is also facing pressure over same-sex marriage and attitudes towards the party's grassroots.
In the letter, the business leaders accuse Eurosceptic MPs of abandoning the national interest in their calls for the UK to leave the EU.
"The economic case to stay in the EU is overwhelming," they wrote.
"To Britain, membership is estimated to be worth between £31bn and £92bn per year in income gains, or between £1,200 to £3,500 for every household.
"What we should now be doing is fighting hard to deliver a more competitive Europe, to combat the criticism of those that champion our departure.
"We should push to strengthen and deepen the single market to include digital, energy, transport and telecoms, which could boost Britain's GDP by £110bn."
The letter's signatories included the current and next presidents of the Confederation of British Industry, the chairmen of BT, Deloitte, Lloyds and Centrica, and Virgin Group boss Sir Richard Branson.
The letter went on: "We should promote the cause of EU membership as well as defend our position.
"The benefits of membership overwhelmingly outweigh the costs, and to suggest otherwise is putting politics before economics."
Former Conservative Foreign Secretary and Chancellor Lord Howe wrote in the Observer on Sunday that Mr Cameron had "opened a Pandora's box" by promising to re-negotiate Britain's membership of the EU.
Lord Howe said the Tory leadership was "running scared" of its backbenchers and had allowed Euroscepticism to "infect the very soul of the party".
But Mr Hunt insisted on BBC One's Andrew Marr Show that the party was "absolutely united" on the issue of Europe and Lord Howe's views did not "represent the reality" of the situation.
Mr Cameron has pledged an in-out referendum on Britain's membership of the EU by the end of 2017 if he wins the next general election.