"The deployment of new missile-defense elements in Europe has the Russian Federation as its aim," Medvedev said at a press conference with German Chancellor Angela Merkel in the Black Sea resort town of Sochi.
The United States and Poland signed an agreement on Thursday to deploy 10 U.S. interceptor missiles in the former Communist-bloc country.
The news comes amid a military crisis in Georgia that has provoked strong criticism of Russia by the United States and other Western countries.
Commenting on the move, Medvedev said: "We will continue working on this issue. We are ready to continue discussing these issues with all the parties."
Moscow's NATO ambassador said earlier on Friday that by signing a missile defense agreement with the United States, Poland has effectively confirmed that the missile shield is aimed against Russia.
"The Poles should be thanked for helping reveal the strategic goal of the U.S. missile defense plan," Dmitry Rogozin said in an interview with RIA Novosti.
A top Russian military official said the Polish-U.S. deal would worsen Russia's relationship with the United States.
"Regrettably, in the extremely difficult situation that has evolved today, the American side is aggravating the relationship between the U.S. and Russia," said Col. Gen. Anatoly Nogovitsyn, deputy chief of the General Staff of the Russian Armed Forces.
Russia is strongly opposed to the missile shield plan, which it says will undermine its nuclear deterrent and threaten its national security.
Washington says plans to place 10 interceptor missiles in Poland coupled with a radar system in the Czech Republic are intended to counter possible attacks from what it calls "rogue states," including Iran.
The agreement was reached after Washington agreed to reinforce Poland's air defenses. The deal is still to be approved by the two countries' governments and Poland's parliament.
Polish Prime Minister Donald Tusk said in televised remarks that "the events in the Caucasus show clearly that such security guarantees are indispensable." The U.S.-Polish missile talks had been dragging for months before recent hostilities in Georgia.
Moscow has accused the West of bias in favor of Georgia and reliance on statements from Tbilisi during the South Ossetia armed conflict. Russia says it deployed additional troops to South Ossetia to reinforce its peacekeepers and protect civilians after Georgia attacked the capital of the breakaway republic on August 8.
Officials say the interceptor base in Poland will be opened by 2012. The Czech Republic signed a deal to host a U.S. radar on July 8.
Russian officials earlier said Moscow could deploy its Iskander tactical missiles and strategic bombers in Belarus and Russia's westernmost exclave of Kaliningrad if Washington succeeded in its missile shield plans in Europe. Moscow also warned it could target its missiles on Poland.