David Cameron has weakened the UK's influence in the European Union and the "aggressive rhetoric" against Brussels could lead to a British exit, Jose Manuel Barroso has said.
The former president of the European Commission said that under the Prime Minister the UK was no longer at the centre of EU decision-making and had lost its position as an important point of contact between the United States and Europe.
The Prime Minister has insisted that the public will be given the opportunity to decide whether to remain in the EU in an in/out referendum by the end of 2017 if he is returned to Downing Street after May's general election.
Mr Barroso said a British exit would be a "real mistake from all points" and warned Mr Cameron against continuing to attack Brussels in the run-up to his promised referendum if he wanted the UK to remain part of the union.
He told BBC Radio 4's World At One: " I think many people that are going to make the case when the time comes, and if there is a referendum, I think the majority will be in favour - at least I hope so.
"But it depends now on leadership in Britain. Frankly, it's not sure because the current situation - putting all the time the blame on Europe - makes it harder.
"You cannot criticise Brussels and the European Union from day one to day six and to ask for people to vote for Europe (on) day seven.
"So the logic of the referendum is a very dangerous logic: it's either yes or no, no maybes.
"I am concerned with the period between now and the moment of the referendum, if there is a referendum, because the aggressive rhetoric can create real damage.
"But I believe what I call the rational, reasonable leaders in Britain will be able to make the positive case for Europe."
Mr Barroso, who was succeeded by Jean-Claude Juncker on November 1, said Mr Cameron had a "difficult relationship" with the EU because of the "pressure" he faced from the Eurosceptics in the Conservative Party.
"I see David Cameron as basically a very pragmatic leader, someone that certainly wants to defend the interests of his country, as previous prime ministers have done.
"But while, with Tony Blair, Britain was really playing a very important role in the European Union, they were at the centre of decisions, today this is no longer the case.
"I think it's a matter for reflection: the American president, if he wants to get European countries on board, I think the first call he makes is the chancellor of Germany, no longer to the British prime minister.
"This is new (and) frankly not very appropriate for Britain to leave the very important position Britain has - or at least had - at the centre of the European Union."
He added: "Britain could be much more influential today if Britain (was) concentrating on a positive agenda. There are a lot of matters where we see eye-to-eye with the British government.
"Unfortunately, because of some exceptionalism that the current leadership in Britain wants to consolidate regarding the European Union, I think the opportunities for more positive, pro-active, leadership have been to some extent spoiled."
Mr Cameron has made curbing immigration the central aim of his renegotiation strategy ahead of the referendum, but Mr Barroso said Europe's leaders would block any attempt to restrict the principle of freedom of movement although there could be support for plans to combat so-called 'benefits tourism'.
He said: "I believe there are very legitimate concerns, not only in Britain, regarding the abuse of benefits because of immigration.
"But those concerns should not put in question the fundamental principle of freedom of movement inside the European Union."
He added: " You have heard the leaders of other countries, from Germany and others, saying clearly that to renegotiate those principles is simply not possible, but to address the issues of concern on abuse of migration, this is certainly possible, I think it would be useful to do it."