David Cameron will highlight the benefits for Britain of a free trade deal between the EU and US as he holds talks with Barack Obama in the White House.
The Prime Minister is to argue that an agreement could be worth up to £10 billion a year to the economy.
However, he could also need to reassure the President about the UK's future within the grouping, amid ongoing Tory skirmishing on the issue.
On Sunday, Cabinet ministers Michael Gove and Philip Hammond became the latest senior figures to indicate they would currently vote to leave the EU - a prospect which alarms the US administration.
Mr Cameron hopes to focus on trade liberalisation, development and Syria during his three-day visit to America, but is unlikely to be able to escape the EU row raging at home.
The two leaders will be joined in the Oval Office by US secretary of state John Kerry, Mr Cameron's national security adviser Kim Darroch, and opposite number Tom Donilon.
The Prime Minister will urge a peace conference on Syria by the end of the month. He believes efforts to end the 27 month conflict have gained some momentum after his trip to Sochi for talks with President Vladimir Putin last week, and Mr Kerry's visit to Moscow. Russian support for Bashar Assad's regime has been one of the main obstacles to easing the situation, but the West has appeared split on whether to respond by arming rebels.
Speaking to reporters on the plane to the US, Mr Cameron struck a positive note on prospects for movement on Syria. He played down apparent differences of approach with Washington, saying there was "very strong unity of purpose between Britain and America that we should be working very closely with the rebels".
"But I think there is also something bigger happening here which is a realisation that it would be far better if what we could do is bring about a political transition through a greater engagement and agreement between America, Russia, Britain, France, other powers," he said. "While it is no secret that Britain and Russia have taken a different approach to Syria I was very struck in my conversations with President Putin that there is a recognition that it would be in all our interests to secure a safe and secure Syria with a democratic and pluralist future, and end the regional instability. We have got a long way to go, but they were good talks."
Mr Cameron will also raise the prospect of using next month's G8 summit in Northern Ireland to launch negotiations for an EU-US trade deal.