Holding Russian and Ukrainian flags, protesters shouted: “The occupation of Crimea is Russia’s disgrace.”
A smaller pro-Moscow rally was being held elsewhere.
Moscow supports the vote, which Ukraine and the West have dismissed as illegal.
Kiev says Russian “provocateurs” are behind clashes eastern Ukraine.
Three people have died in Ukraine in pro- and anti-Moscow rallies in the cities of Donetsk and Kharkiv with sides blaming each other.
Russia’s military intervention in the Crimean peninsula – part of Russia until 1954 and host to its Black Sea fleet – followed the fall of Ukraine’s pro-Moscow President Viktor Yanukovych on 22 February.
Ukraine’s interim President Oleksandr Turchinov echoed the charge, saying “Kremlin agents” were organizing and funding the protests in eastern Ukraine.
Moscow denies this, vowing to protect its “compatriots” from far-right radicals.
Up to 50,000 people attended the rally in Moscow to oppose the government’s intervention in Crimea and eastern Ukraine.
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