The 11th round of discussions, to be held in Miami, will address a still-substantial list of differences on key issues between the two sides, after more than two years of talks on the ambitious Transatlantic Trade and Investment Partnership.
But they come after Washington scored a major triumph with the agreement two weeks ago to set up a Pacific free trade group with Japan, Canada and nine other countries.
Both groupings aim at broadly lowering trade tariffs and non-tariff barriers, a relatively small issue between the United States and Europe, where trade taxes are already very low.
But they also aim higher, at setting what the White House calls the rules for 21st century trade and investment, with a special focus on digital trade and intellectual property issues, and on harmonizing regulations for global business.
A deal would tie together two giant economies that are home to some 850 million people and account for about half of global output.