The simultaneous protests organized by Get Out Of Nuclear, a collective made up of hundreds of associations, was intended to raise the prominence of the issue in the run-up to April-May presidential elections. Smaller-party candidates resolutely opposed to the construction of new facilities called European pressurized-water reactors joined the protesters.
The nation must "get out of the nuclear business" and "invest in renewable energies like solar energy or wind power," said Olivier Besancenot of the Radical Communist League, marching with protesters in the western city of Rennes.
Organizers claimed the number of protesters in Rennes was 30,000 to 40,000. Police estimated the crowd at 10,000.
There were also protests, with estimated crowds ranging from 4,000 to 9,000 people, in Lyon, Toulouse, Lille and Strasbourg.
The most nuclear energy-dependent country in the world, France has dozens of reactors churning out most of its electricity.
The first EPR is to be built in Flamanville, in northern France, and would be operational by 2012 - when the new president's five-year mandate ends.
Electricite de France, the state electrical company, has said the reactor would pave the way for other plants to adopt the more efficient pressurized-water technology by 2020.
Socialist candidate Segolene Royal, whom polls place second behind the conservative Interior Minister Nicolas Sarkozy, has said she would "open the debate" on EPR construction should she win, but made no yes-or-no commitment. Sarkozy has not directly addressed the issue.