"Riot police, showered with stones and paint bombs, used pepper spray to prevent the protesters breaking into the ECB. Several protesters were injured and police made some arrests, though they gave no numbers.
"The aim of this blockade is to prevent normal operations at the ECB," said Blockupy spokesman Martin Sommer, adding that some people who had tried to come to work had been sent home by the protesters.
Demonstrators brandished signs with slogans such as "Humanity before profit" and some held up inflatable mattresses with the slogan "War Starts Here" written on them.
Trucks with water cannons stood by and a helicopter hovered overheard.
Europe's Blockupy movement was formed after the Occupy Wall Street movement in 2011.
One of the protesters, Lena Turowski, a 25-year-old student of international development, condemned European governments' embrace of austerity measures to repair their economies.
"At the moment, they are trying to fight the crisis with the same measures that caused the crisis. And the people are being forgotten about," she told Reuters.
"It is also about solidarity with those who are being affected by austerity and crises in their countries," she said"
Hundreds of protesters spread through Frankfurt, to retail shops and even the airport in a prelude to rallies planned for June 1st all across Europe.
Friday's anti-austerity actions were similar to the anti-capitalist demonstrations about a year ago in Frankfurt, when police detained hundreds of people for defying a temporary ban on the protests. Blockupy received permission from the court to hold the protest, however the ruling limited the number of protesters to 200.