More than 15,000 protesters converged on the streets of the nation's capital Chisinau to rally against the government and demand early elections.
"The people are with us. They do not want to support oligarchs and the criminal authorities," opposition leader Andrei Nastase told protesters, according to the AFP news agency.
The protesters braved sub-zero temperatures to decry dwindling living standards in the ex-Soviet country, saying the ruling government uses pro-European rhetoric to disguise widespread corruption.
Moldova signed an historic EU association agreement in 2014 despite staunch opposition from Russia.
Demonstrators are particularly enraged at the disappearance of some $1.5 billion (1.39 billion euros) from three of the country's banks prior to parliamentary elections in 2014.
On Wednesday, protesters stormed parliament after a new pro-European government was approved. The country's pro-Russian and pro-Western forces have been known to suspend their differences to challenge the country's ruling elite amid the political crisis.
The Moldovan parliament has until January 29 to form a new government or it will be dissolved, a key demand of the protesters.
Since demonstrations erupted in 2014, the ex-Soviet nation has had five prime ministers.
ls/jlw (AP, AFP)