Czech police estimated attendance at some 70,000 whereas organizers put it at over 100,000, Czech TV reported.
Protesters from the opposing sides of the political spectrum called on the coalition government of liberal-conservative Prime Minister Petr Fiala to cap soaring prices or stand down.
Some groups also urged the government to bypass the EU to negotiate energy supply deals directly with Russia and called for military neutrality. The Czech Republic is a member of both the EU and NATO.
Petr Fiala said people had a right to protest but claimed that demonstrators were being manipulated by "pro-Russian forces." Interior Minister Vit Rakusan said the government took public concerns seriously.