The UK would be left "alone" and "powerless" if it votes to leave the European Union, putting the "special relationship" with the United States in jeopardy, Nick Clegg has warned.
On the eve of Barack Obama's visit to the UK, where is he expected to caution against Brexit, the former Deputy Prime Minister said "if we leave Europe behind, America may leave us behind too".
In a speech at Princeton University in the USA, Mr Clegg said the only prominent American who did not support the UK remaining in the EU was Republican presidential hopeful Donald Trump.
The former Liberal Democrat leader said during his time in government he was told "over and over again by US decision makers" that British influence in the EU "strengthened the West" and the co-operation between the EU and Nato.
He highlighted recent interventions in support of the UK's membership of the EU by Washington's ambassador in London Matthew Barzun, secretary of state John Kerry and former State Department spokesman James Rubin.
"And, most importantly, President Obama has said that having the UK in the European Union gives the States 'much greater confidence about the strength of the transatlantic union'. It is a case I hope and expect he will make loudly and clearly when he visits London in the coming days.
"In fact, the only prominent American who has dissented from that view is Donald Trump.
"So, the choice for any British voter who cares about American opinion couldn't be clearer: Trump wants Britain out of the EU; President Obama wants us to stay in. It is one of the more remarkable twists in this ongoing saga that Boris Johnson, a contender for the future leadership of Britain's most Atlanticist political party, should side with Trump rather than Obama. I know who's side I - and I suspect millions of other Brits - would rather be on."
Mr Clegg added: "Britain and the United States will always be cousins, but we may not always be partners. If we leave Europe behind, America may leave us behind too.
"By walking away from the top table of European affairs, we cede our influence and our importance.
"That's why I believe that leaving the European Union will have an unravelling effect on all our most important relationships. With our neighbours in Europe. With our cousins in America. And even with our brothers and sisters within the United Kingdom if it pushes Scotland closer to independence.
"We will be left with no empire, no union and no special relationship. We will never have been so alone. Never so isolated. Never so powerless."
In a sign of the importance the Remain camp are putting on Washington's views, both David Cameron and George Osborne both tweeted messages welcoming the intervention by eight former US treasury secretaries warning against Brexit.
Vote Leave's chief executive Matthew Elliott dismissed Mr Clegg's speech: "Voters will be in no mood to be lectured by a politician with more broken promises than there are Lib Dem MPs left in Parliament."