Thousands of people have marched in the German city of Hannover against a proposed Transatlantic Trade and Investment Partnership (TTIP) deal.
They say the deal would drive down wages, and weaken environmental protection and labour rights.
US President Barack Obama - who is pushing hard for the agreement - says it would create millions of jobs and increase trade by lowering tariffs.
On Sunday, he will visit the northern city to open a huge trade fair.
German police estimate that more than 30,000 took part in the peaceful protest rally in Hannover.
Many carried placards with slogans that read: "Stop TTIP!"
The demonstrators have also been voicing their anger over the secrecy surrounding the ongoing TTIP negotiations.
"The TTIP between the American continent and Europe is very dangerous for the democracy, for our nature and for the rights of the workers," protester Florian Rohrich told the BBC.
"The rights in America for workers are much lower. It's like the Trojan horse. They can't change our whole system. But they will - because TTIP is written by the groups, by the companies, not by the politicians," he added.
The negotiations were launched three years ago, and the next round is due to open on Monday in New York.
Defending the TTIP, President Obama has said that the agreement would mean "new growth and jobs on both sides of the Atlantic".
The TTIP aims to cut tariffs and regulatory barriers to trade between the US and EU countries, making it easier for companies on both sides of the Atlantic to access each other's markets.
Industries it would affect include pharmaceuticals, cars, energy, finance, chemicals, clothing and food and drink.
What is TTIP for?
The aim is to boost the economies of the EU and the US by removing or reducing barriers to trade and foreign investment.
How would TTIP work?
By eliminating almost all tariffs (taxes applied only to imported goods) on trade between the US and the EU.
Why is TTIP controversial?
Much of the concern is about the regulatory aspect: that it would lead to lower standards of consumer and environmental protection and safety at work.